To analyze the efficacy and safety of the combination of mometasone furoate cream and tretinoin cream in the treatment of chloasma. Methods A total of 70 patients with chloasma admitted to the Second Affiliated Hospital of Air Force Medical University from January to December 2022 were randomly divided into control group and observation group, with 35 patients in each group. The control group was treated with vitamin A acid cream, and the observation group was treated with mometasone furoate cream combined with tretinoin cream. The symptom scores, clinical efficacy, quality of life and adverse reactions were compared between the two groups. Results After treatment, the symptom score of the observation group was lower than that of the control group (P <0.05). The total effective rate of treatment in the observation group was 94.29%, which was higher than 74.29% in the control group (P <0.05). After treatment, the scores of quality of life in the observation group were higher 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 The combination of tretinoin cream and mometasone furoate cream has a good effect in the treatment of chloasma, which can improve their clinical symptoms and quality of life. At the same time, the combined application has high safety and will not increase the risk of adverse reactions.