The severe storm is expected to cross the WA coast as a category four system northeast of Port Hedland near Eighty Mile Beach early on Friday.
It was confirmed as a category-three cyclone, when 370km northwest of Broome, according to the Bureau of Meteorology.
An alert is in place for Bidyadanga to De Grey in the Kimberley and Pilbara regions.
Abnormally high tides, destructive winds and up to 400mm of rain are forecast as Ilsa moves southwest and turns towards the Pilbara coast.
"The very destructive core of Ilsa, with extreme gusts up to 270 km/h, is expected to cross the coast between De Grey and west of Bidyadanga," the bureau warned.
Communities from Broome to Marble Bar and Whim Creek have been warned to be ready for cyclonic weather.
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.
The Port Hedland port is being cleared of vessels including iron ore carriers.
Ilsa is forecast to maintain tropical cyclone intensity into Friday as it tracks inland to Telfer and moves east.
Ilsa is expected to be 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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