Later, the temple flourished to the extent of controlling 86 branch temples of Hongan-ji Temple in the Yoshino region, and when Hongan-ji Temple clashed with Nobunaga ODA in the Sengoku period (Period of the Warring States), Honzen-ji Temple also leading its followers into battle against the Ishiyama Hongan-ji Temple.
その後、吉野地方の本願寺末86ヶ寺を束ねて隆盛を得たが、戦国時代に入り本願寺が織田信長と対立すると、本善寺も門徒を率いて石山本願寺攻めに応戦。