The Austrian opened the race in 56.92 seconds. Felix Neureuther of Germany was 0.38 behind to become the only racer within a second of the lead.
Luca Aerni of Switzerland, who started 27th, finished 1.36 behind in third, closely followed by Fritz Dopfer of Germany and Alexis Pinturault of France, who won the slalom in Wengen last week.
"Visibilty was obviously bad," said Hirscher, who wiped his goggles immediately after crossing the finish line.
Michael Janyk of Whistler, B.C., was the top Canadian in 17th place.
Mario Matt of Austria skied out in the first run, which means Hirscher will remain in the lead of the slalom standings regardless the outcome of the second run. Hirscher is aiming to become the first slalom skier to win back-to-back crystal globes since Thomas Sykora in 1997 and '98.
It's the final slalom before nations have to name their Alpine skiing teams for the Sochi Olympics.
After days of mild weather, course workers salted the piste in order to harden up the surface, but the fresh snow made for difficult conditions. Furthermore, the unusual placing of some gates by Croatian coach Ante Kostelic made racing even harder.
"On such a tough course the field gets torn apart," Hirscher said.
Kostelic, the father of former overall champions Ivica and Janica, has made a name for setting challenging courses. A year ago in Kitzbuehel, the jury rejected a course set by Kostelic, deeming it as "unskiable."
The course wasn't that extraordinary this time, though Neureuther said it was "by far the most difficult slalom in Kitzbuehel I have ever done."
"Visibility is brutal, the course setting is extreme, and the piste is bad," the German said. "It's extreme but we are the best ski racers so we have to adapt to these conditions. I managed that quite well in the first run. I think nobody feels really well today."
Nolan Kasper of the United States lost a pole when he tried to clean his goggles during the final part of his run. He still completed the final gates and came 3.34 seconds behind in 25th place.
"It's definitely tough, it's one or two gates in a row that get a lot of splashback," Kasper said. "It's not the snow falling, it's the snow from the gate. That's why I tried to wipe my goggles and dropped my pole. I am probably not going to do that next run."
The second run will be held under floodlights later Friday.