Inter, who dropped to 12th in the Italian Serie A table following Sunday's 1-0 loss to Sampdoria, said youth team coach Stefano Vecchi would be in charge of the team for Thursday's Europa League match at Southampton.
"The club thanks Frank and his staff for the work they have undertaken at the and wish them the best for the future," Inter said in a statement.
Inter, traditionally one of Italy's three biggest clubs alongside Juventus and city rivals AC Milan, appointed the 46-year-old De Boer on August 9, two weeks before the start of the season, after Robert Mancini left by mutual consent.
The former Netherlands defender had no experience of playing or coaching in Italy. He had previously been in charge of Dutch side Ajax Amsterdam for six years during which he won four league titles.
His overall record of five wins, two draws and seven defeats included shock losses to Hapoel Beer Sheva and Sparta Prague in the Europa League and at home to Cagliari in Serie A.
Image: Frank de Boer
Photograph: Alessandro Garofalo
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