The Bureau of Meteorology upgraded the cyclone to a category-four system on Thursday morning with gusts near the centre up to 230km/hr as it tracks toward the coast 290km north of Port Hedland.
Port Hedland mayor Peter Carter said residents were preparing for the impact of the cyclone, with evacuation centres set up in the town.
"Everyone is on edge," Mr Carter told ABC TV on Thursday.
"They understand that cyclones are what they are. They're very, very unpredictable."
The category-four system is expected to cross the WA coast northeast of Port Hedland near Eighty Mile Beach late on Thursday or early on Friday.
Mr Carter urged people to watch out for household objects turning into flying debris.
"All our residents are basically putting away their barbecues and outdoor furniture," he said.
He added loose objects travelling at high speeds had the potential to become "missiles in the air."
Mr Carter said evacuation centres had been set up for people who did not feel safe in their homes in Port Hedland.
"Port Hedland is a very transient town. We have people from overseas who don't understand what cyclones do," he said.
"It's not a normal storm. These things hang around for two or three hours and have very destructive winds."
Communities from Bidyadanga to Whim Creek, including Port Hedland and inland to Marble Bar, Nullagine and Telfer have been urged to move their vehicles under cover and keep their emergency kits on hand.
Abnormally high tides, destructive winds and up to 400mm of rain are forecast.
The BOM warned that the "very destructive" part of Ilsa, with extreme gusts up to 275 km/h, could impact the area between De Grey and west of Bidyadanga.
Workers and tourists at Eighty Mile Beach caravan park and nearby Wallal Downs cattle station are being evacuated, along with non-critical workers at Newcrest's Telfer mine and BHP's sites across the region.
Extra emergency workers, essential supplies and aircraft have been sent to the area as authorities warn the North West Coastal Highway could close between Port Hedland and Broome due to flooding.
Port Hedland is being cleared of ships, including iron ore carriers.
Communities from Beagle Bay to Broome have been given the all-clear, but have been asked to watch out for residual damage, including fallen trees and power lines.
Ilsa is forecast to maintain tropical cyclone intensity into Friday as it tracks inland to Telfer and moves east.
The system is expected to weaken below tropical cyclone strength overnight on Friday before moving east into southern parts of the Northern Territory.
It is the first category-four system to strike the region in almost a decade.
The last, named Tropical Cyclone Christine, crossed the coast southwest of Port Hedland in December 2013.
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