The likelihood of paediatric cancer patients experiencing oral mucositis has increased significantly as high-dose and multiple chemotherapy agents are used in the treatment of childhood cancer in recent years. The resulting oral ulcerative lesions can cause significant pain, dysphagia, alteration in nutritional status and increased risk for localized infections that could disseminate systemically. The purpose of this pilot study was to determine the clinical benefits of an oral care protocol intervention on the prevention and reduction of the severity of oral mucositis in paediatric patients receiving chemotherapy. Fourteen children were enrolled in the study; there were seven children in the control and seven in the experimental group. In the experimental group, children received a preventive oral care protocol consisting of tooth brushing, normal saline rinse and 0.2% chlorhexidine mouth rinse. Children in the control group received usual care according to the study's clinical setting. Data were collected at baseline, then twice a week for 3 weeks. The incidence of ulcerative lesions, severity of oral mucositis and the related pain intensity were used as the main outcome variables. The experimental group exhibited fewer and less painful oral mucositis lesions. The results of this study support the preventive use of oral care protocols in paediatric patients undergoing chemotherapy for cancer treatment.