A major thoroughfare in Melbourne's CBD has been closed off after a deadly tiger snake was seen slithering into a gutter, forcing police to establish a large cordon around it.

Police officers and City of Melbourne animal handlers were guarding the scene at the corner of Spencer and Collins streets just after midday on Thursday as they waited for a snake handler to arrive.

As more police arrived, crime scene tape was strung up around the snake.

One southbound lane outside the Quality Hotel was also closed.