Objective To explore the efficacy and safety of different concentrations of 5-fluorouracil (5-FU) combined with compound betamethasone in the treatment of pathological chest scar. Methods A total of 80 patients with pathological chest scar (hypertrophic scar and keloid) admitted to Guizhou Aerospace Hospital from September 2023 to September 2024 were selected, and they were divided into the low-concentration group, the medium-concentration group, the medium-high-concentration group and the high-concentration group by the random number table method, with 20 patients in each group. The four groups were injected with 5-FU and compound betamethasone suspension at concentrations of 6.3 mg/ml, 12.6 mg/ml, 25.2 mg/ml and 50 mg/ml respectively. The clinical efffcacy, Vancouver Scar Scale (VSS) score and adverse reaction rate were compared among the four groups. Results There were signiffcant differences in the total effective rate among the four groups at 1 year after injection (P<0.05). The total effective rate of the high-concentration group was higher than that of the low-concentration group and the medium-concentration group (P<0.05). There was no signiffcant difference in the total effective rate between the high-concentration group and the medium-high-concentration group (P>0.05). There were signiffcant differences in VSS scores among the four groups at 1 year after injection (P<0.05). The VSS score of the high-concentration group at 1 year after injection was lower than that of the low-concentration group and the medium-concentration group (P<0.05). There was no signiffcant difference in VSS scores between the high-concentration group and the medium-high-concentration group at 1 year after injection (P>0.05). There were no signiffcant differences in the incidence of acne, folliculitis and adverse reactions among the four groups (P>0.05). There were signiffcant differences in the incidence of hematopoietic system inhibition and adverse reactions among the four groups (P<0.05). Conclusion Medium-high concentration and high concentration of 5-FU combined with compound betamethasone achieve good clinical efficacy in the treatment of pathological chest scar and can effectively improve scar symptoms. However, the high-concentration group has a higher incidence of hematopoietic system inhibition and adverse reactions, without increasing the risk of other adverse reactions.