The 32-year-old unsurprisingly started in between the sticks for the lunchtime kickoff at Selhurst Park, but deep into the second half, he dropped to the turf after kicking the ball out of play.
Alisson appeared to be clutching the back of his thigh and was visibly angered at his latest blow, slamming the ground in frustration and letting out a scream as the medics attended to him.
The ex-Roma man eventually rose to his feet and limped off the field to be replaced by Vitezslav Jaros, who came on for his first senior appearance for the Reds due to the absence of regular number two Caoimhin Kelleher.
Arne Slot will be expected to deliver an update on Alisson's injury at the end of the game, but the 32-year-old's reaction was highly worrying, and he has been increasingly bedevilled by injuries over the past couple of seasons.
Alisson missed September's 3-0 win over Bournemouth due to a thigh problem, and a similar issue ruled him out for two months last season, as he missed 15 games for club and country between February and April.
The South American is still under contract at Liverpool for three more seasons, but his number one spot could come under threat when Giorgi Mamardashvili arrives from Valencia next summer.