Police called to a shopping centre in the Maaleh Adumim settlement found "a 47-year-old man, a guard at the mall, lying on the ground with multiple stab wounds on his body," a police statement said.
"It appears that this was a (Palestinian) nationalist-motivated attack," it said, adding that in response the settlement had been closed to entry for Palestinians until Sunday.
"According to security cameras a man of seemingly Arab apparence, carrying a knife and an axe, was seen fleeing the scene," the statement said.
Jerusalem's Hadassah hospital said in a statement that the man was undergoing surgery.
"He is in very serious condition and his life is in danger," it said in a statement.
A wave of Palestinian knife, gun and car-ramming assaults that erupted in October has claimed the lives of 28 Israelis, as well as an American, a Sudanese and an Eritrean.
The violence has also seen 176 Palestinians killed by Israeli forces, most while carrying out attacks but others during clashes and demonstrations.
Maale Adumim, with a population of about 36,000, is one of the largest Israeli settlements in the occupied West Bank.
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