Objective To study the application effect of type A botulinum toxin injection combined with hyaluronic acid filling in facial wrinkle reduction. Methods A total of 82 females who underwent facial wrinkle reduction in Nanjing Mebel Beauty Hospital from January 2023 to June 2024 were selected. According to the random number table method, they were divided into the control group (40 females) and the observation group (42 females). The control group was treated with hyaluronic acid filling, and the observation group was combined with type A botulinum toxin injection on the basis of the control group. The VISIA characteristic scores, skin elasticity, skin tightness and adverse reactions were compared between the two groups. Results The scores of purpura, pore, texture, wrinkle and pigmentation in the observation group were lower than those in the control group, and the differences were statistically significant (P <0.05). After treatment, the scores of skin elasticity and skin tightness in the observation group were higher than those in the control group, and the differences were statistically significant (P <0.05). The incidence of adverse reactions in the observation group was 4.76%, which was lower than 10.00% in the control group, but the difference was not statistically significant (P >0.05). Conclusion The application of type A botulinum toxin injection combined with hyaluronic acid filling in facial wrinkle reduction can better improve the wrinkle reduction effect and enhance the facial aesthetics compared with the simple application of hyaluronic acid filling, and it will not increase the incidence of adverse reactions.