Watch: Scream VI: Official trailer
The Heroes actress, 33, appeared in Scream IV in 2011 and her character Kirby Reed was a favourite with fans of the grisly franchise.
Kirby was left for dead after being stabbed but has recovered and is back to battle the baddie once again.
The trailer sees Ghostface terrorising sisters Sam and Tara (Melissa Barrera and Jenna Ortega) in New York after they fled Woodsboro.
He stalks them through the city, terrorising them in their homes and in one scene hunts them down on a subway.
The creepy killer manages to hide as it appears to be Halloween and several other people on the train are wearing Ghostface outfits.
But as one moves closer, they realise it's him.
The trailer also gives fans a glimpse of Friends star Courteney Cox, who is reprising the role of investigative reporter Gale Weathers.
In one terrifying scene she takes a call from Ghostface in her apartment, before he suddenly bursts in through a window.
He flees into a cupboard and she grabs a gun, firing shots into the door before apparently realising she's out of bullets.
One Scream star who isn't in the movie is Neve Campbell, who revealed last year that she would not be reprising the role of Sidney.
She told People at the time: "I did not feel that what I was being offered equated to the value that I bring to this franchise, and have brought to this franchise, for 25 years.
"And as a woman in this business, I think it's really important for us to be valued and to fight to be valued."
Scream VI is released on 10 March.