Just after he killed his younger brother Fuyuyasu ATAGI because of slanders from Hisahide MATSUNAGA in 1564, he died on August 20 in a house near Kawachi Imoriyama Castle due to extended illness, passed at a time when it seemed as if he was following his brother (There are opinions that it was an assassination, rather than a death from illness. Hisahide MATSUNAGA and three other people from the Miyoshi family are suspected; however, this theory is believed to be a myth created by writers in later years).
永禄7年（1564年）5月、松永久秀の讒言を受けて弟・安宅冬康を誅殺した直後、元々前年から病がちだったため、自身も後を追うように7月4日に河内飯盛山城下の屋敷において病死した（病死ではなく謀殺説もあり、犯人は松永久秀や三好三人衆の中の誰かではないかと推測し、俗説もしくは後世の作家の創作だとも考えられている）。