After internecine strife within the Ashikaga family blossomed into outright opposition between Takauji and his younger brother Tadayoshi ASHIKAGA in what became known as the Kanno Disturbance, Tadayoshi's adopted son Tadafuyu ASHIKAGA sought refuge in Kyushu in 1349, and Yorinao chose to back Tadafuyu, giving him his own daughter in marriage and falling into armed conflict with Noriuji ISSHIKI, the Kyushu tandai (military commissioner) and the force of Ashikaga in Kyushu, but Tadafuyu was destroyed, and consequently the greater part of Yorinao's territory was confiscated.
足利家で尊氏と弟の足利直義が対立した観応の擾乱が発生し、1349年（貞和5年/正平(日本)4年）に直義の養子の足利直冬が九州へ逃れると頼尚は娘を娶せて直冬を擁立し、九州における足利勢力である九州探題の一色範氏と争うが、直冬が没落したために領地の大半は没収される。