Spurs are currently fifth in the Premier League and level on points with fourth-placed Chelsea, but have played a game more than the Blues.
However, Holtby is confident that Spurs can beat last year's champions in Sunday's match at White Hart Lane.
"It will be a tremendous game on Sunday," Holtby told the club's official website. "City have just reached the final of the FA Cup and these six games are our cup finals, starting against City.
"They are a side full of quality players but we're determined to get three points, especially at home. It would be a massive win for us.
"The fans were brilliant out in Basel and that's what we need again now on Sunday.
"Everything has to work - the team, the fans, all connected together - and I know everyone is right up for it."
Holtby joined Spurs from German side Schalke 04 in January.