It is the first time since 2012 that Shiffrin finishes outside the top 30 in a World Championship race and does not qualify for the second round.
Shiffrin has previously stated that she suffers from mental problems when she is to compete in her former specialty, after the severe crash in Killington in November.
"I'm still not myself", the American wrote on Instagram ahead of Friday's competition.
Shiffrin had planned to make a comeback in giant slalom at the World Championship but postponed it to the World Cup weekend in Italian Sestriere.
There, she has now delivered two consecutive disappointments.
First, 25th on Friday, and then 33rd on Saturday.
With 99 World Cup victories in her career, Mikaela Shiffrin is the most victorious skier of all time.
The trophy cabinet also includes two Olympic gold medals and eight World Championship gold medals – the latest in the team combination in Saalbach a week and a half ago.
