Objective: To explore the effect of evidence-based collaborative care model on oral mucositis in patients with radiotherapy and chemotherapy tumors. Methods: Ninety-six patients undergoing primary radiotherapy and chemotherapy in Department of Oncology from January 2016 to January 2017 were divided into a control group and an observation group, each with 48 cases. The control group used basic oral care measures. The observation group established a collaborative group of care and maintenance, clearly synergize care goals and formulate evidence-based “synergic care plans for oral mucositis in patients undergoing radiotherapy and chemotherapy”. The average of oral condition scores, pain scores, and oral health-related quality of life scores within 1 year, the first 3 days, the end of the day, 14 days after chemotherapy were compared between the two groups. Results: Based on evidence-based collaborative care model, patients could improve their oral status, relieve pain, and improve their oral health-related quality of life (P<0.05) on day 3 and day 14 after radiotherapy and chemotherapy. Conclusion: The evidence-based collaborative care model has good results in the prevention and treatment of oral mucositis in patients with radiotherapy and chemotherapy tumors. It can be widely used in the clinic in the future and continuously update research evidence to improve clinical nursing programs.