"There was an accident this morning, it's serious, there are injured," a police spokeswoman told AFP, without providing other details.
The collision occurred at around 6.45am near the train station of Rafz, a town some 30 kilometres (19 miles) north of Zurich, overturning train carriages, local media reported.
The locomotive on one of the trains was smashed in, with broken glass and twisted metal visible through a gaping hole in the side.
The train derailed, and several of its carriages tipped on the side.
Ambulances have rushed to the scene and service on the train line between the towns of Bulach and Schaffhausen has been suspended, with a bus replacement service available.
Currently five people have been confirmed injured, one seriously, according to a statement from Zurich cantonal police.
However a rescue worker told newspaper 20 Minutes that there could be as many as 49 injured.
“Ambulances from all over the region have been mobilized,” he said.
While the reason for the accident is not yet known, an 18-year-old passenger on one of the trains told 20 Minutes that he thought his train, which had just left Ratz in the direction of Schaffhausen, went through a red signal.
“A fast train from Zurich came up behind us and brushed against the side of our RER. The Intercity derailed.”
Passengers were evacuated quickly, he added.
Meanwhile Lars Fehr, 20, told the Blick daily he had been sitting in the Rafz station waiting room when the crash occurred.
"Suddenly there was a loud bang," he told the paper, adding that both the trains had been heading in the same direction.
Fehr said a woman had called the police and some people had headed out to the derailed train to help.
"The conductor got out of the locomotive, put on a safety vest and helped passengers out of the train," he said.
Interruption: Rafz (SBB CFF FFS): 20.02.2015 00:00 – 10:59Interruption: La gare Rafz sur la ligne Bülach – Sch… http://t.co/F68464e7yc
— Railinfo CFF (@railinfo_cff) February 20, 2015
— Zürcher Unterländer (@ZUnterland) February 20, 2015