Hirscher, who returned from retirement to represent the Netherlands at the World Cup opener in Soelden, Austria after a five-year absence, tore his ACL and injured his outer capsule apparatus during training on the Reiteralm on Monday.
"Of course, it's a tough cut after eight months of a heartfelt project and a huge pity, because the whole team, including me, we all had other plans for this winter," Hirscher said in a statement.
"It will certainly be hard to watch the races... As is unfortunately the case with skiing - part of the game. Maybe I'm finally done with my journey.
"For the first time, I'm experiencing the painful issue of cruciate ligaments first-hand, which so many have already had to go through... I would like to thank everyone who made this incredible journey possible and accompanied me on it."
Hirscher's team Van Deer said the Austrian will remain under observation in hospital for two to three days.
Hirscher has won a record eight consecutive overall World Cup titles from 2012 to 2019, along with seven World Championship gold medals and two Olympic triumphs.