Hiddink, whose career has included spells in charge of the Dutch and Russian national teams and periods at PSV Eindhoven, Chelsea and Real Madrid, joined Anzhi in 2012 and is leaving just two games into the season after a defeat by Dynamo Moscow.
"I always said my tenure at Anzhi could end when the club was able to develop and grow by itself without my involvement," Hiddink said in a statement on the club's website (www.fc-anji.ru).
"Now the time has come. I am convinced that the club has a great future."
Fellow Dutchman Rene Meulensteen, a former first team coach at Manchester United, will succeed Hiddink as manager, the club said.
In May, Anzhi denied media rumours that they were about to part company with 66-year-old Hiddink, saying they were satisfied with his work with a team that features the likes of Cameroon striker Samuel Eto'o.
The club from the volatile North Caucasus region, bankrolled by billionaire owner Suleiman Kerimov, have taken only one point from their opening two league games of the season and Hiddink's departure comes after Friday's 2-1 defeat at Dynamo Moscow.
Anzhi, who finished third in the Russian Premier League last term, reached last season's Russian Cup final where they were beaten on penalties by CSKA Moscow.
Hiddink has been one of a number of names linked with the vacancy at Spanish champions Barcelona, who are looking for a new coach after Tito Vilanova stepped down last week as he continues treatment for throat cancer.
(Reporting by Alessandra Prentice; Additional reporting by Maxim Rodionov; Editing by Justin Palmer and Sonia Oxley)
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