The Russians have never lost to Portuguese opposition and can put four points between themselves and the reigning Primeira Liga champion.
Luciano Spalletti's side has not lost in all 10 of its home fixtures in all competitions, with seven of them ending in victories.
As a result, the club sits three points clear at the top of the Russian Premier League, with the goals of Danny and Hulk crucial.
Midfielder Danny has netted 12 this season - already three times more than he scored last term - while former Porto forward Hulk has weighed in with nine, including two in the Champions League.
Zenit sits second in Group G and has already beaten one side from Portugal this season, toppling Pacos de Ferreira 8-3 on aggregate in the playoffs for Europe's premier club competition.
The result of this match will be vital in determining the outcome of the group, with Zenit and Porto set to battle it out for second place behind runaway leader Atletico Madrid.
The Russian giant has never lost to a Portuguese side, winning four matches and drawing one, including a 3-1 win over Porto in the group stage of the 2011-12 competition.
Spalletti will demand more from his side than it has showed in the last two encounters though.
The team was knocked out of the Russian Cup last week, defeated 2-0 at second-tier FC Tyumen in the round of 32, while it was held to a 1-1 league draw by Amkar Perm on Saturday.
The club will take heart from its 1-0 win at Porto last month, though, with Aleksandr Kerzhakov's goal - which was scored with five minutes left - his 27th in Europe.
Belgium midfielder Axel Witsel will sit out the match through suspension, while Vyacheslav Malafeev has recovered from a calf injury but is unlikely to start.
Porto also tops its league by three points, having posted seven wins and two draws from its first nine matches of the Primeira Liga season.
Paulo Fonseca's side was held to a 1-1 draw at Belenenses on Saturday, with Eliaquim Mangala's strike canceled out by Joao Pedro.
Porto is taking part in its 18th Champions League campaign - only Manchester United has played in the tournament more times - and boasts victories in four of its five trips to Russia in the competition.
The club is unbeaten in an incredible 52 Primeira Liga matches, with its last defeat - which came against Gil Vicente in January 2012 - the only loss in 108 attempts.
Colombian Jackson Martinez topped the scoring charts in Portugal with 26 goals last term and he is in good form for Porto - who will miss the suspended Hector Herrera - again this season with nine strikes so far.