Police are searching for a suspect who slashed the throat of homeless man while he was sleeping in Sydney's CBD.

The victim was sleeping on the footpath with another homeless man when the attacker crouched over him and slit his throat yesterday, police said.

Officers said the 37-year-old suffered a "substantial" wound.

He was taken to St Vincent's Hospital where he underwent emergency surgery. He is currently in a stable condition.

The suspect was last seen running east on Wynyard Street towards George Street.

He was described as wearing a dark hooded top and jeans.

Haymarket Foundation chief executive officer Mat Flynn urged people who live on the street to stay in groups for protection.

"It's a heinous attack on some of the most vulnerable people in our community, absolutely cowardly," he said.

"Sadly, we do see people who do live rough are often victim of crimes and this is just an outrageous crime against our most vulnerable."

Police have warned the city's homeless community to be vigilant and urged members of the public to look out for suspicious behaviour around people sleeping on the streets.