Objective To analyze the effect of 308 nm excimer laser combined with halometasone cream on skin lesion-related indicators and quality of life in patients with vitiligo. Methods A total of 60 patients with vitiligo admitted to our hospital from August 2023 to August 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with halometasone cream, and the observation group was treated with 308 nm excimer laser combined with halometasone cream. The clinical efficacy, skin lesion-related indicators and quality of life were compared between the two groups. Results The total effective rate of the observation group was 93.33%, which was higher than 73.33% of the control group (P<0.05). After treatment, the pigmentation score, skin lesion area and VASI score of the observation group were better than those of the control group (P<0.05). After treatment, the scores of all DLQI items in the observation group were lower than those in the control group (P<0.05). Conclusion The combination of 308 nm excimer laser therapy and halometasone cream for the treatment of vitiligo demonstrates deffnite clinical efffcacy, which can promote pigment recovery, reduce skin lesion area and improve quality of life.