Objective To explore the application effect of hyaluronic acid filling combined with botulinum toxin in neck rejuvenation. Methods A total of 74 patients with neck aging who underwent rejuvenation treatment in our hospital from September 2020 to September 2022 were selected as the research objects. According to the random number table method, they were divided into control group and combined group, with 37 cases in each group. The control group was treated with hyaluronic acid filling, and the combined group was treated with botulinum toxin combined with hyaluronic acid filling. The neck stripe grading and Antera depression volume, clinical efficacy, pain degree, side effects and satisfaction were compared between the two groups. Results After treatment, the neck grading and Antera depression volume of the two groups were lower than those before treatment, and those in the combined group were lower than those in the control group (P<0.05). The total effective rate of treatment in the combined group was 89.19%, which was higher than 67.57% in the control group (P<0.05). There was no significant difference in VAS score and total incidence of side effects between the two groups (P>0.05). The satisfaction scores of patients, third parties and operators in the combined group were higher than those in the control group (P<0.05). Conclusion Hyaluronic acid filling combined with botulinum toxin can improve the therapeutic effect of neck rejuvenation, and improve patient satisfaction and cosmetic effect without increasing pain and side effects.