The midfielder was hauled off early on in the Schwarzgelben's clash with Augsburg on Saturday, but the extent of his injury will not be known until Sunday.
The Poland international, 28, was substituted in the first 10 minutes of the Schwarzgelben's opening match of 2014, following the month-long winter break in the Bundesliga.
At first it was not clear what the wide midfielder had injured after twisting his leg on the field of play, but the club confirmed that Kuba had seriously injured his knee and could be a major doubt for the remainder of 2013-14.
"Jakub Blaszczykowski must expect the worst. The Pole has possibly suffered a tear of his anterior cruciate ligament in the Bundesliga match against Augsburg," the BVB website wrote on Saturday after the clash at Signal Iduna Park had finished.
"After two minutes of football, Blaszczykowski got stuck in the turf in a challenge which sidelined him. An accurate diagnosis cannot be made until Sunday though."
Jurgen Klopp's men have been desperately unlucky with injuries this season, with Kuba the latest in a string of players - including Marcel Schmelzer, Mats Hummels and Ilkay Gundogan - to be sidelined as the team bids to rejuvenate a Bundesliga campaign which sees it 14 points behind league leader Bayern Munich.