The Reds moved into third in mid-week after Chelsea's shock home defeat to Bournemouth, coupled with their away victory over Huddersfield Town the previous night.
Fifth-placed Spurs meanwhile comprehensively beat Manchester United, in second, with a sublime performance at Wembley Stadium to sit two points adrift of fourth.
A win on Merseyside - where they have only won two of their past 25 visits in the Premier League - would allow them to leapfrog Liverpool and put them in a strong position to compete for second - the same position they finished in last term.
But defeat would leave them five points adrift of Jürgen Klopp's men and eight points behind United, while Arsenal won convincingly on Saturday and Chelsea are likely to bounce back from defeat against an out-of-sorts Watford on Monday night.
With just 13 top-flight matches remaining after this weekend, a five-point advantage - were Liverpool to triumph over the Lilywhites - could prove potentially key, particularly with Spurs' schedule congested by being involved in three competitions.
This is the 150th league meeting between the two clubs and rarely have they both been on such level standing - with failure to acquire a top-four finish a huge disappointment for either.
Liverpool come into this particular clash looking to exact revenge for their 4-1 Wembley defeat to the North London side earlier this season.
Spurs ruthlessly exposed Liverpool's defensive weaknesses on that afternoon, though Klopp's charges also constantly shot themselves in the foot, as they produced one of their best performances under Mauricio Pochettino.
Liverpool went 18 games unbeaten off the back of that and despite back-to-back defeats at the end of January, they will hope to prove those losses were only minor setbacks with a statement triumph over their rivals.
The league's two top goalscorers also go head-to-head in this clash, with 21-goal striker Harry Kane the only player to net more in the top flight in the current campaign than Liverpool winger Mohamed Salah, on 19 after the same amount of appearances.
They are the jewels in each team's glistening crowns but are far from the only capable match winners, with Spurs boasting the trio of Christian Eriksen, Heung-min Son and Dele Alli and Liverpool's Salah supported by the star-studded cast of Sadio Mané and Roberto Firmino.
Just as it was in the clash between league leaders Manchester City and Liverpool at Anfield last month, everything seems set up for a breathless blockbuster between two of the league's best attacking units - and whoever comes out on top will hope they can use it as a foundation to finish at least fourth.
Midfielder Adam Lallana is not expected to be involved for Liverpool with a muscle injury despite returning to full team training on Friday.
In defence, Ragnar Klavan remains unavailable due to a minor thigh strain but January signing Virgil van Dijk could return to the starting line-up after being benched for the win at Huddersfield.
Nathaniel Clyne is stepping up his recovery from a long-term back injury but will be sidelined for the next few weeks at least, with Liverpool otherwise having a fully-fit squad to choose from.
Visitors Tottenham welcome Serge Aurier and Harry Winks back to their squad having overcome respective calf and ankle injuries to return to training this week.
Toby Alderweireld could potentially make a return from a serious hamstring problem that has kept him out of Spurs' last 19 matches across all competitions and will be assessed late on.
Left-back Danny Rose is also back training alongside his team-mates after knee-related problems and was on the bench against United. He could feature for the first time since Boxing Day here.
Mauricio Pochettino suggested that Lucas Moura - signed for £28 million from Paris Saint-Germain on deadline day - will not be involved having played just once since November 4.
Recent form (all competitions)
Tottenham Hotspur: WWDDW
Huddersfield Town 0-3 Liverpool
Tottenham Hotspur 2-0 Manchester United
Liverpool have only lost one of their last 23 home Premier League games against Tottenham (W15, D7) - that sole defeat coming in May 2011.
Spurs have not done the league double over their Merseyside opponents since the 2010-11 campaign.
Liverpool are unbeaten in 14 Premier League matches at Anfield - winning eight - since being beaten 2-1 by Crystal Palace back in April.
The Reds have not lost a league game at Anfield against a top-six rival since defeat to Manchester United in January 2016, winning six and drawing six of 12 matches since then.
Mohamed Salah could become the first Liverpool player ever to score 20 Premier League goals in less than 27 games (Fernando Torres and Daniel Sturridge), with 19 in 24 so far.
Roberto Firmino has scored eight goals and laid on three assists in his last 11 league games since the start of December.
Spurs have earned seven points from nine in their last three Premier League away games, coming after a run of just one point from 15 before that.
Harry Kane has scored four goals and laid on two assists in six Premier League appearances against Liverpool.
The England international also has 18 goals in his last 13 top-flight away games.
Jonathan Moss will oversee his 19th Premier League fixture of the season, having so far issued 70 yellow cards, two red cards and five penalties in 18 games so far.
The 47-year-old oversaw Liverpool's 5-0 defeat at Manchester City in September, when Sadio Mané was sent off for a high boot, as well as Spurs' defeat away at United.
The experienced Sunderland-born official was the man in the middle for his first Premier League game back in December 2010 and has since refereed the FA Cup final.