However, the Miyoshi Sanninshu, who felt Hisahide's power was threatening, invaded to the Yamato Province in cooperation with the local samurai of the Yamato Province, including Junkei TSUTSUI who was drifting after Hisahide took over the Tsutsui-jo Castle (at the Battle of Tsutsui-jo Castle), and tried to kill Hisahide.
しかし久秀の勢力を危険視した三好三人衆は、永禄の変から7ヶ月ほどたった12月、かつて久秀に筒井城を奪われて（筒井城の戦い）放浪していた筒井順慶ら大和の国人衆らと手を結んで大和に侵攻し、久秀を討とうとした。