Police blocked the road in both directions after the woman, who was in her 50s, was hit by a car around 12.05 p.m.
She has been taken to hospital with serious injuries, police said.
Drivers are encouraged to avoid the area and Blackpool Transport is redirecting its bus links.
A police spokesman said: “Please note that Talbot Road, Blackpool is closed in both directions due to a road traffic collision.
“Please avoid the area where possible. Thank you for your patience.”