Objective To study the application effect of carbon dioxide (CO2) fractional laser combined with sodium hyaluronate solution on patients undergoing facial wrinkle removal. Methods: Seventy-five patients who received facial wrinkle removal treatment in the Burn and Plastic Surgery Department of our hospital from September 2023 to September 2024 were selected as the research subjects. The research subjects were divided into the control group (37 cases) and the observation group (38 cases) according to the random number table method. The control group was treated with sodium hyaluronate solution. The observation group was treated with CO2 fractional laser combined with sodium hyaluronate solution. The dermal thickness, facial wrinkles, overall facial cosmetic effect, growth factor [vascular endothelial growth factor (VEGF), basic fibroblast growth factor] levels and the incidence of adverse reactions of the two groups were analyzed and compared. Results: Two months after treatment, the dermal thickness of both groups was significantly increased compared with that before treatment, and the absolute fraction value of wrinkles was significantly decreased compared with that before treatment. Moreover, the dermal thickness of the observation group after treatment was significantly higher than that of the control group, and the absolute fraction value of wrinkles was significantly lower than that of the control group (P < 0.05). The overall facial cosmetic improvement rate of the observation group was significantly higher than that of the control group (P < 0.05). Two months after the treatment, the levels of VEGF and bFGF in both groups were significantly increased compared with those before the treatment, and the levels of VEGF and bFGF in the observation group after treatment were significantly higher than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: CO2 fractional laser combined with sodium hyaluronate solution can reduce facial wrinkles in patients undergoing facial wrinkle removal, increase the thickness of the facial dermis, regulate the level of growth factors, enhance the overall facial cosmetic effect, and has a relatively high treatment safety.