must be translated as "gel" Objective: To evaluate the application effect of cross-linked hyaluronic acid composite microspheres in the treatment of mid-face rejuvenation patients. Methods: A retrospective analysis was conducted on the clinical data of 68 mid-face rejuvenation patients admitted from January 2025 to October 2025, who were divided into two groups (34 cases each) based on different treatment protocols. The control group received cross-linked hyaluronic acid sodium gel injections, while the observation group received cross-linked hyaluronic acid composite microsphere filling. The clinical efficacy, skin indicators, visual analog scale (VAS), transepidermal water loss (TEWL), stratum corneum water content, and epidermal sebum content were compared between the two groups. Results: The total effective rate of the observation group was higher than that of the control group (P<0.05). Postoperatively, the observation group exhibited lower pigmentation, wrinkles, texture, and pore size compared to the control group (P<0.05). Immediately after surgery and at 30 minutes postoperatively, the VAS score of the observation group was lower than that of the control group (P<0.05). Postoperatively, the observation group had lower TEWL and higher stratum corneum water content and epidermal sebum content than the control group (P<0.05). Conclusion: Cross-linked hyaluronic acid composite microspheres for mid-face rejuvenation therapy can achieve threefold benefits of volume filling, skin texture improvement, and pain control simultaneously, demonstrating greater advantages in aesthetic effects and treatment experience compared to cross-linked hyaluronic acid sodium gel injections.