Objective To explore the effect of hyaluronic acid filling in hand rejuvenation treatment. Methods A total of 200 patients planned to receive hand rejuvenation treatment admitted to the Department of Aesthetic Surgery, Suzhou Lingmei Oriental Medical Beauty Clinic from May 2023 to December 2024 were selected, and they were divided into the control group and the observation group according to different intervention methods, with 100 patients in each group. The control group was treated with autologous fat granule transplantation, and the observation group was treated with hyaluronic acid filling. The improvement of surgical rejuvenation, satisfaction, adverse reactions and hand skin quality were compared between the two groups. Results There was no statistically significant difference in the hand rejuvenation effects between the two groups (P >0.05). The satisfaction of the observation group (94.00%) was superior to that of the control group (85.00%) (P <0.05). The incidence of adverse reactions in the observation group was lower than that in the control group, but the difference was not statistically significant (P >0.05). The scores of moisture content, fineness and texture of the observation group after treatment were higher than those of the control group (P <0.05). Conclusion Both hyaluronic acid filling and autologous fat granule transplantation can effectively improve hand aging in patients, with high safety. However, hyaluronic acid filling is more helpful to improve patient satisfaction and achieve better hand skin quality after treatment.