Objective To explore the application effect of cross-linked hyaluronic acid composite microsphere fflling therapy in midface rejuvenation. Methods A total of 68 patients who underwent midface rejuvenation at Quanzhou Fengze Vsangel Medical Aesthetic Clinic from January to October 2025 were selected, and they were divided into the control group and the observation group according to different treatment regimens, with 34 patients in each group. The control group was treated with cross-linked sodium hyaluronate gel injection, and the observation group was treated with cross-linked hyaluronic acid composite microsphere fflling. The clinical efffcacy, skin texture indicators, skin barrier function and pain intensity were compared between the two groups. Results The total effective rate of treatment in the observation group was 100.00%, which was higher than 82.35% in the control group (P<0.05). After 50 days of operation, the VISIA scores of pigmentation, wrinkles, texture and pores in the observation group were lower than those in the control group (P<0.05). After 50 days of operation, the TEWL of the observation group was lower than that of the control group, and the stratum corneum hydration and epidermal sebum content were higher than those of the control group (P<0.05). The immediate and 30-min postoperative scores of VAS in the observation group were lower than those in the control group (P<0.05). Conclusion Compared with cross-linked sodium hyaluronate gel, cross-linked hyaluronic acid composite microsphere fflling therapy can effectively optimize midface rejuvenation effect, and improve facial aging manifestations and skin barrier function, with milder pain sensation.