OHP got called out after 10 o'clock for an accident on I-35 near milemarker 33 in Ardmore.
"We received a call of an accident where a vehicle was southbound in the northbound lanes," said Trooper Ken Duncan.
Troopers with the Oklahoma Highway Patrol said 19-year-old Peyton Karlik was driving south in the northbound inside lane when she struck the cab of a semi.
Troopers said the driver of the semi tried to avoid the crash by swerving but ended up hitting a pickup in the outside lane.
Authorities said Karlik was taken by helicopter to Plano Medical Center with head and internal injuries.
"She did not appear to be wearing her seatbelt which could've greatly contributed to the injuries that were received," said Duncan.
OHP said no one else was hurt.
The interstate was closed for more than 3 hours.
Investigators are trying to figure out why Karlik entered the wrong side of the freeway.