Honjō Hidetsuna served as a bushō during the Sengoku and Azuchi-Momoyama periods. He was a retainer of the Uesugi clan of Echigo Province. Hidetsuna served as the lord of Tachio Castle.
Hidetsuna was born as the son of Honjō Saneyori, a bushō and retainer of the Uesugi clan. Together with his father, Hidetsuna served Uesugi Kenshin, a daimyō and deputy shōgun of the Kantō. Hidetsuna, similar to Saneyori, was deeply trusted by Kenshin. In 1559, when Kenshin traveled to Kyōto meet Ashikaga Yoshiteru, the thirteenth shōgun of the Muromachi bakufu, Hidetsuna carried his long sword for him. In 1572, during an offensive in Etchū Province, Hidetsuna was ordered by Kenshin to serve as the commander in charge of Kasugayama Castle.
In 1575, Hidetsuna, along with Uesugi Kagenobu and Jōjō Masashige, were assigned to defend Numata Castle in Kōzuke Province and served in battles in the Kantō area.
The death of Kenshin in 1578 led to a succession struggle between two of his adopted sons known as the Otate Conflict. In this event, Hidetsuna joined the side of Uesugi Kagetora. Kagetora was the natural son of Hōjō Ujiyasu and, in 1569, adopted by Kenshin. He was opposed by Uesugi Kagekatsu, the natural son of Nagao Masakage. At this time, Hidetsuna had been staying in the Uesugi residence, and just before its fall, he fled. Thereafter, Hidetsuna joined with Kanamari Chikatsuna, the lord of Sanjō Castle, to resist Kagekatsu, but, on 4/22 of Tenshō 8 (1580), after the fall of Tachio Castle, he headed toward Aizu. Later, he is said to have served Sassa Narimasa.