Objective To explore the effect of carbon dioxide laser combined with photodynamic therapy on DLQI score and safety in patients with condyloma acuminatum. Methods A total of 80 patients with condyloma acuminatum who received treatment in the Department of Dermatology, Taizhou People's Hospital from January 2022 to December 2023 were selected. According to different treatment methods, they were divided into the control group and the observation group, with 40 patients in each group. The control group was treated with carbon dioxide laser, and the observation group was treated with carbon dioxide laser combined with photodynamic therapy. The clinical efficacy, recurrence, human papillomavirus (HPV) load, Dermatology Life Quality Index (DLQI) score and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 95.00%, which was higher than 77.50% in the control group (P <0.05). The recurrence rate at 3 months after treatment and the total recurrence rate in the observation group were lower than those in the control group (P <0.05), but there was no significant difference in the recurrence rate at 6 months after treatment between the two groups (P >0.05). The HPV load and DLQI score in the observation group at 6 months after treatment were lower than those in the control group (P <0.05). The incidence of erythema and edema in the observation group was higher than that in the control group, while the incidence of scarring was lower than that in the control group (P <0.05). There was no significant difference in the incidence of pain and pruritus between the two groups (P >0.05). Conclusion Carbon dioxide laser combined with photodynamic therapy has a good clinical effect, which can not only effectively reduce the recurrence rate, but also decrease the viral load and improve the patient's quality of life score, with high safety.