The forward pulled up with a hamstring injury during last week's 1-0 home win over Swansea City.
The England fringe man has been one of the Hammers' best performers in an up and down season.
But whatever happens they will have to make do without Antonio. "It is a significant injury, he is out for the season," Bilic said.
Michail Antonio has been ruled out for the rest of the season Premier League table based on 2017 results Mon, April 10, 2017
How would the Premier League table look if just results from 2017 counted?
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20. Sunderland (6 points from 12 games) W:1 D:3 L:8 G/D -14
"It's a big blow, he is one of our best players."
Captain Mark Noble begins a two-match ban but Bilic was confident Andy Carroll, Sam Byram and Aaron Cresswell would be passed fit for the Black Cats clash.
Bilic added: "It's a big game for us, Sunderland are desperate for a win and we are looking to win to secure or get closer to securing safety.
"Every win gives you a boost, especially after five defeats in a row. The confidence is back but the belief was permanent and we never lost it."
Andy Carroll could return for West Ham's clash with Sunderland
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Bilic has also had to contend with yet another manager being linked with his job, with Fulham's Slavisa Jokanovic the latest name on the list.
He said: "I know Slavisa, we are from the same region and speak the same language. I like him as a person and as a manager but I am not bothered.
"I don't talk to the owners about every name that appears in the papers."