The Red Devils will take on Manchester City at the Etihad Stadium in the Premier League on December 9.
"It's going to massive game, although it won't decide the title or anything," Smalling told The Mirror.
"But it could go a long way in terms of, mentally, how teams cope and whether they win or lose in the subsequent games.
"We'll be hoping we can go into that game all firing and give them something to really worry about."
United are currently two points clear of City at the top of the league table.