Objective: To investigate the clinical efficacy of halometasone cream combined with urea cream in the treatment of chronic eczema, and analyze its regulatory effects on serum inflammatory factors and skin ceramide levels in patients. Methods: The study included 70 patients with chronic eczema admitted to our dermatology department from March 2023 to March 2024. The patients were divided into two groups using a random number table method: the observation group (35 cases) received treatment with halometasone cream combined with urea cream; The control group (35 cases) only used halometasone cream. The treatment course is all 4 weeks. Compare and analyze the overall efficacy, changes in Eczema Area and Severity Index (EASI) and Visual Analog Scale (VAS) for itching before and after treatment, serum inflammatory factors (interleukin-4 (IL-4), tumor necrosis factor alpha (TNF - α), interleukin-17 (IL-17), interferon gamma (IFN - γ)) levels, and relative levels of skin ceramides between the two groups, while recording adverse reactions. Results: The total effective rate of the observation group was higher than that of the control group (P<0.05); After 4 weeks of treatment, both groups showed a decrease in EASI and itch VAS scores compared to the treatment group, with the observation group being lower than the control group (P<0.05); After 4 weeks of treatment, IL-4, TNF - α, IL-17, and IFN - γ in both groups decreased compared to the treatment group, with the observation group showing a greater decrease than the control group. The relative content of skin NC increased, with the observation group showing a greater increase than the control group (P<0.05); After 4 weeks of treatment, IL-4, TNF - α, IL-17, and IFN - γ in both groups decreased compared to the treatment group, with the observation group showing a greater decrease than the control group. The relative content of skin NC increased, with the observation group showing a greater increase than the control group (P<0.05); There was no significant difference in adverse reactions between the observation group and the control group (P>0.05).Conclusion: The combination of halometasone cream and urea cream is more effective in treating chronic eczema than using halometasone cream alone, and can more effectively alleviate clinical symptoms. Its mechanism may be related to significantly downregulating serum inflammatory factor levels and repairing the key component of the skin barrier, ceramide, with good safety.