Objective To study the application value of gentamicin sulfate combined with hypertonic sodium chloride mixture in the treatment of skin eczema. Methods From November 2020 to January 2024, 80 patients with skin eczema who were treated in the Shihudang Town Community Health Service Center, Songjiang District, Shanghai were randomly divided into control group and study group, with 40 patients in each group. The control group was treated with gentamicin sulfate wet compress, and the study group was treated with gentamicin sulfate + hypertonic sodium chloride mixture wet compress. The levels of inflammatory factors, clinical efficacy, disease recurrence rate and disappearance time of symptoms were compared between the two groups after treatment. Results After treatment, the levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the study group were lower than those in the control group (P <0.05). The total effective rate of treatment in the study group was 97.50%, which was higher than 85.00% in the control group (P <0.05). The recurrence rate of the study group was 2.50%, which was lower than 15.00% of the control group (P <0.05). The regression time of skin lesions and pruritus in the study group was shorter than that in the control group (P <0.05). Conclusion The wet compress of gentamicin sulfate combined with hypertonic sodium chloride mixture can effectively reduce the inflammatory factor indexes of patients with skin eczema, improve the clinical efficacy, reduce the recurrence rate of the disease, and accelerate the regression of clinical symptoms, which is worthy of reference.