The aim of the study was to investigate the application of hydrocolloid dressings in the prevention and treatment of infant diaper rash. A total of 210 infants with diaper rash were included in the study and randomized into 3 groups of 70 infants. Infants in group A received hydrocolloid dressings and individualized nursing; infants in group B received mupirocin plaster and topical application of pearl powder as well as routine nursing; and infants in group C received zinc oxide plaster and routine nursing. The clinical efficacy, incidence of adverse events, time to resolution of diaper rash, hospitalization duration, mean cost and satisfaction of nursing were compared between the 3 groups. After 1 cycle of treatment and nursing, the difference in the healing rate of mild diaper rash between groups A, B and C was significant (P<0.05), with the best healing rate in group A. Differences in the healing rate of grade I and II diaper rash between groups A, B and C was significant (P<0.05), with the best healing rate in group A. The incidence of adverse events in infants between groups A, B and C were significantly different (P<0.05), with the lowest incidence in group A (2.9%). The time to resolution of diaper rash, hospitalization duration and cost in infants were not significantly different (P<0.05). The satisfaction rate of nursing for the parents of groups A, B and C was 98.6, 87.1 and 80.0%, respectively (P<0.05). Hydrocolloid dressings combined with individualized nursing may prevent and treat infant diaper rash effectively, decrease the incidence of adverse reactions significantly, shorten time to resolution of diaper rash and hospitalization duration, reduce mean hospitalization cost, improve parent satisfaction and promote nursing-patient harmony. Thus, this method of treatment was worthy of clinical application.