The Germany international is expected to be sidelined for up to four weeks with knee and ankle problems.
Hummels was only drafted back into Dortmund's plans on Saturday, for a 2-1 defeat to Schalke.
He is, however, heading back to the treatment table at a crucial stage of the season.
The 24-year-old is to sit out important Bundesliga fixtures, as Dortmund chase a top-two finish, and faces a race against time to play any part in the UEFA Champions League quarter-finals.
Dortmund boss Jurgen Klopp admits Hummels' setback could not have come at a worse time.
He told Sky Deutschland: "This is bitter news for us as a club and for him as a player.
"For us as a club, it's the worst news we could have received at this point in time.
"When he suffered the injury it didn't look that bad. Unfortunately it was."