Objective To investigate the advantages of tacrolimus ointment combined with carbon dioxide fractional laser in the treatment of vitiligo. Methods A total of 80 patients with vitiligo in Zhen'an County Hospital from January 2019 to March 2021 were randomly divided into routine group and experimental group, with 40 cases in each group. The conventional group was treated with tacrolimus ointment, and the experimental group was treated with carbon dioxide lattice laser on the basis of the conventional group. The effective rate, serum inflammatory factor levels (tumor necrosis factor-α, interferon-γ, interleukin-17) and adverse reactions were compared between the two groups. Results The total effective rate of the experimental group was 97.50%, which was higher than 80.00% of the conventional group (P＜0.05). After 6 months of treatment, tumor necrosis factor-α, interferon-γ and interleukin-17 in the experimental group were lower than those in the conventional group (P＜0.05). The tatal incidence of adverse reactions in the experimental group was 5.00%, which was lower than 25.50% in the conventional group (P＜0.05). Conclusion Tacrolimus ointment combined with carbon dioxide dot matrix laser has obvious therapeutic effect, and has an ideal intervention effect on vitiligo.