Background: This study assesses the effect of oral cryotherapy on the incidence and severity of chemotherapy-induced oral mucositis in combined chemotherapy regimens.Methods: This was a randomized controlled trial that enrolled 80 cancer patients. We evaluated the primary oral status of all patients prior to chemotherapy. Patients were divided into two groups, experimental and control. The experimental group was given ice to place in their mouths from 5 min before to 5 min after chemotherapy.The control group received no intervention. Both groups were treated with the following chemotherapy regimens: i) 5- fluorouracil + leucovorin; ii) cyclophosphamide + adriamycin + 5-fluorouracil; or iii) cyclophosphamide + methotrexate + fluorouracil. World Health Organization and patient-based oral mucositis scales were used for evaluation.Results: According to the WHO based Oral Mucositis Scale, the incidence of oral mucositis in the intervention group (45%) was significantly lower than the control group (77.5%; P=0.01). The incidence of oral mucositis in the intervention group based on the Patient-Judged Oral Mucositis Scale was lower than the control group. The findings of this study indicated that patients who underwent cryotherapy had less severe oral mucositis based on both WHO (P=0.01) and patient oral mucositis scales (P=0.001).Conclusion: Oral cryotherapy because of its ease of application, tolerability and lack of side effects makes it an important resource for reducing the incidence and severity of oral mucositis. The role of oncology nurses is crucial to the application and success of oral cryotherapy.