The Germanwings passenger jet had been travelling from Barcelona to Dusseldorf, French officials said.
Eric Ciotti, the head of the regional council, said search and rescue teams are heading to the crash site at Meolans-Revels.
The French newspaper La Provence, citing aviation officials, said the Airbus plane carried at least 142 passengers, two pilots and four flight attendants.
In a live briefing, Mr Hollande said the area of the crash was remote and it was not clear whether anyone on the ground had been hurt.
He added that it was probable that a number of the victims are German.
“It’s a tragedy on our soil,” he said, adding he would be speaking shortly with German chancellor Angela Merkel.
The plane left Barcelona just after 10am local time and had been due to arrive in Dusseldorf at 11.49am local time.
It is thought the flight became lost on radar at 6,800ft (2,073m).
Germanwings is a lower-cost unit of Lufthansa, Germany’s biggest airline.
It has been operating since 2002 as part of traditional national carriers’ response to the rise of European budget airlines. It serves mainly European destinations.
The area where the plane went down is near a popular ski resort.
The German federal bureau of aircraft accident investigation is sending three people to France to join the investigation, spokesman Germout Freitag said.
French interior minister Bernard Cazeneuve, the country’s top security official, is heading to the crash site.
French interior ministry spokesman Pierre-Henry Brandet said debris from the crash has been located, with the plane having crashed at an altitude of 6,500ft in the Alps.
He said the plane sent out a distress signal at 10.45am local time (9.45am GMT). The passenger manifest is currently being verified.
Mr Brandet told BFM television he expects “an extremely long and extremely difficult” search and rescue operation because of the area’s remoteness.
Captain Benoit Zeisser of the Digne-le-Bains police said conditions had been cloudy, but the cloud ceiling was not low and there did not appear to have been turbulence.
He told a French TV network he could not comment yet on the state of the debris site.
The UK’s deputy Prime Minister Nick Clegg said: “My heart goes out to the family and friends of those people who appear to have lost their lives in this devastating air crash in the Alps.”
