The passenger plane crashed into the remote Zagros mountains, with the nearest city being Semirom in Isfahan province.
Witnesses told local media the plane, said to have children on board, was trying to make an emergency landing on a pasture before it crashed in the Dena mountain range.
The plane vanished about 20minutes after taking off from Mehrabad Airport at 5.50am local time.
It was flying between Tehran and the south-western city of Yasuj.
Bad weather is hampering rescue efforts
An emergency services spokesman said: “All emergency forces are on alert.
“The plane had 50 to 60 passengers.”
The plane is from Iran Aseman Airlines, according to local media, and is a ATR 72.