The Tigers, who ran riot at Cardiff last time out, recorded a 3-2 victory at St James' Park in September and a win this Saturday could push them into the top half of the table.
Steve Bruce's side won 3-2 at St James' Park in September, and three points on Saturday would secure a quadruple of Premier League victories over teams from the northeast, with Sunderland having also been beaten home and away.
Last weekend's 4-0 thumping of Cardiff City lifted Hull to 11th in the table, six points clear of the bottom three, and another win could see it climb into the top half if West Ham fails to beat Everton.
With the bottom half of the division becoming increasingly congested, Bruce knows Hull needs to continue picking up positive results in their battle to avoid relegation back to the Championship.
Hull should head into the game with confidence, having followed up their win at Cardiff with a 2-1 victory in Monday's FA Cup fifth-round replay with Brighton.
However, after a strong start to the season at the KC Stadium - which saw them lose just one of their opening eight top-flight home games - Hull are winless in three games on home soil since the turn of the year.
Newcastle, meanwhile, will be hoping to claim a first league win over Hull since March 1990, although the clubs have only met five times in league competition since then.
Alan Pardew's team have fared well away this season, with six wins from 13 matches, although they were on an alarming sequence of four games without a point or a goal before last Sunday's 1-0 win over Aston Villa.
Newcastle currently sits eighth on 40 points and has slipped 10 points behind fifth-placed Tottenham in the race for European qualification.
Hull's Paul McShane is out with a long-term ankle injury, but Bruce is hopeful Tom Huddlestone, Liam Rosenior and Alex Bruce will all have recovered from knocks in time for the game.
Meanwhile, Newcastle midfielder Sylvain Marveaux is available after being left out against Villa, although Davide Santon and Hatem Ben Arfa are both out with knocks.