The 23-year-old went down in the 27th minute at Anfield without contact, clutching his lower right leg before being carried off on a stretcher and replaced by Mohamed Salah. Liverpool manager Arne Slot said after the match that the injury looked serious, and Deschamps has now ended any uncertainty about the striker's participation in the tournament.
In a statement, the France head coach said: "Hugo suffered a serious injury on Tuesday evening against PSG. The severity of his injury will unfortunately prevent him from finishing the season with Liverpool and participating in the World Cup."
"Hugo is one of the dozen young players who have made their debuts with the national team in recent months. He had perfectly integrated into the group, both on the pitch and off it."
"This injury is a huge blow for him, of course, but also for the France team. His disappointment is immense. Hugo will regain his top form, I'm convinced of it."
"But I wanted to express all my support to him, as well as that of the entire staff. We know he'll be fully behind the France team, and we're all thinking of him very strongly."
Ekitike had been firmly established in Deschamps' plans for the tournament after a breakthrough debut season in the Premier League. He scored in France's 2-1 friendly win over Brazil in March and had made eight international appearances in total. L'Équipe has reported a nine-month recovery timeline, which would rule him out until early 2027 and cost him the opening months of next season at Anfield as well.
Liverpool signed Ekitike from Eintracht Frankfurt for £69 million last summer. He has scored 17 goals in all competitions this season.