Objective To observe the application effect of Yiqi Huoxue Quban decoction combined with hydroquinone cream in the treatment of melasma of qi deficiency and blood stasis type. Methods A total of 80 patients with melasma of qi deficiency and blood stasis type admitted to Zhongshan Torch Development Zone People's Hospital from March 2023 to April 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 40 patients in each group. The control group was treated with hydroquinone cream, and the observation group was treated with Yiqi Huoxue Quban decoction combined with hydroquinone cream. The clinical efficacy, skin lesion area and skin lesion color, skin condition, oxidative stress indexes and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 90.00%, which was higher than 70.00% in the control group (P <0.05). After treatment, the skin lesion area score, skin lesion color score, skin elasticity score, skin moisture content, SOD and NO in the observation group were all better than those in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion In the treatment of melasma of qi deficiency and blood stasis type, the combined treatment of Yiqi Huoxue Quban decoction and hydroquinone cream can not only improve the skin lesion area, skin lesion color, and oxidative stress response, but also enhance the treatment effect and has high safety.