This study aims to explore the clinical efficacy and safety of Compound Oleum Lithospermi in alleviating objective skin symptoms and subjective tingling/itching of chronic cheilitis exfoliativa.Methods:A total of 124 patients with chronic cheilitis exfoliativa who were treated in the Outpatient of Dermatology Department，Dongfang Hospital，Beijing University of Chinese Medicine from February 2019 to December 2020 were randomized into experimental group(52 cases)，control group(48 cases)，and placebo group(24 cases) with the random number table method.The experimental group was coated with Compound Oleum Lithospermi，the control group with Kangfuxin solution，and the placebo group with ordinary sesame oil.The objective skin symptoms(area，burning sensation，erosion，scaling，crusting，fissuring) were observed and Visual Analog Scale(VAS) score of subjective tingling/itching was calculated.Adverse reactions were recorded.Results:The total effective rate for the objective skin symptoms was 94.20% in the experimental group，as compared with the 58.40% in the control group and 37.50% in the placebo group(P<0.05).As for self-perceived symptoms，the effective rate in the experimental group was 80.80%，higher than the 60.40% in the control group and 66.6% in the placebo group(P=0.078>0.05).Conclusion:Compound Oleum Lithospermi can effectively improve the objective skin symptoms and subjective tingling/itching of patients with chronic cheilitis exfoliativa，with low occurrence of adverse reactions.