The robber targeted Jazzy's newsagents, in Netherhill Road, Gallowhill, Paisley, at about 21:00 on Thursday.
After the cash was handed over, a struggle broke out between the two men, leaving the worker with hand injuries.
The suspect then ran off towards Netherhill Crescent. Police have appealed for information.
The suspect is described as white, aged around 30, about 5ft 9in tall, with a medium build and an "acne-scarred complexion".
At the time of the robbery, he was wearing a black and white jacket, with a scarf and had his hood up over a baseball cap.
Det Insp Suzie Chow said: "This was a very traumatic experience for the shop assistant who did everything he could to foil this robbery and luckily without sustaining any serious injuries.
"Inquiries so far have revealed that there were several girls hanging around near to the shop at this time and I urge them to contact police immediately as they may be able to provide valuable information that could assist our investigation.
"We also know that a man was also seen nearby at this time and it is vital that we speak to this man as soon as possible."
The man seen nearby is described as white, around 26 to 27 years old, 5ft 10in tall and of slim build.
He was wearing a white jacket with black stripes and hood. He wore his hood up and also wore a scarf.
A shopkeeper suffered cuts to his hand after struggling with a thief who threatened him with a knife before fleeing with a four-figure sum of cash.