A man in his 20s has died in hospital following a home invasion in the Perth suburb of Mount Lawley overnight.

Key points: Two men entered the house before getting into an altercation with those inside

Two men entered the house before getting into an altercation with those inside One intruder was fatally wounded while the second fled the scene and is at large

One intruder was fatally wounded while the second fled the scene and is at large Police have urged anyone with information about the incident to come forward

It is believed the deceased was with another man and was armed with a knife when he entered a house near the intersection of Stanley Street on Guildford Road about 1:45am.

A WA Police spokesman said it appeared there was an altercation with four occupants of the home and the man was seriously wounded.

He was taken to Royal Perth Hospital where he later died, sparking a murder inquiry.

"Homicide Squad detectives now have carriage of this investigation," police said in a statement.

Police cordoned off Stanley Street and part of Guildford Road after the home invasion. ( ABC News: James Carmody )

Two of the occupants of the home were taken to Sir Charles Gairdner Hospital with less serious injuries.

The second suspected intruder fled the scene and remains at large.

The four-lane Guildford Road was closed in both directions for several hours on Friday morning as more than a dozen detectives gathered evidence as part of their investigation.

The crime scene stretched more than 100 metres along the road, with investigators focusing their attention on a number of different points where blood stained the road.

Police have urged anyone with any information about the incident to call Crime Stoppers on 1800 333 000.