Emergency services arrived at the alumina site in Oakley at 3:30pm on Tuesday, after reports of a number of workers had suffered chemical burns.
A man believed to be in his 30s and a man in his 60s were raced to the nearby Fiona Stanley Hospital where they are still receiving medical treatment for non life-threatening injuries.
Three other workers were also injured but did not require hospitalisation.
In 2014 another employee was also hospitalised after a toxic spill broke out on the site.
In a statement about the emergency on Tuesday, Alcoa confirmed “a chemical spill occurred at its Pinjarra Alumina Refinery this afternoon and several people were impacted”.
“Alcoa’s focus and thoughts are with the injured people and their families,” the statement said.
“The company is working with authorities and a full investigation will be undertaken.”
WorkSafe WA are preparing to send a team to the site on Wednesday morning to investigate, while the cause of the spill remains unknown.
The Pinjarra Refinery, located 95km south of Perth, is one of the largest alumina refineries in the world and produces 4.7 million metric tons of product each year.
The site opened 60 years ago and currently employs 4500 people, with 1160 employees located on site.