Objective To investigate the clinical efficacy of CO₂ fractional laser combined with hydrocortisone butyrate cream in the treatment of senile chronic eczema. Methods A total of 82 elderly patients with chronic eczema in our department from January to November 2020 were selected and divided into control group and experimental group according to different treatment methods, with 41 cases in each group. The control group was treated with hydrocortisone butyrate cream for first-line treatment, and the experimental group was treated with CO₂ fractional laser on the basis of the control group. The curative effect, itching degree, skin lesion severity, cytokine level, quality of life and adverse reactions were compared between the two groups. Results The effective rate and IFN-γof the experimental group was higher than that of the control group, and the VAS score, EASI score, IL-4, IL-10 and DLQI score were lower than those of the control group (P＜0.05). In the experimental group, three patients showed redness and swelling in the lesion area after treatment, and one patient showed dotted bleeding points in the lesion area after treatment, all of which spontaneously. Conclusion CO₂ fractional laser combined with hydrocortisone butyrate cream is safe and effective in the treatment of elderly patients with chronic eczema, which can significantly reduce the degree of pruritus and skin lesion severity, improve the level of cytokines, improve the quality of life, and help to recover as soon as possible. It has clinical application significance.