Background: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands, accounting for approximately one-third of all salivary gland tumors. Based on the proportion of epidermoid and mucous cells, MEC is classified into three grades. High-grade MEC, an extremely rare malignancy, has a higher proportion of epidermoid cells and a poorer prognosis. Currently, there has been no standard treatment for patients with positive surgical margins after parotidectomy. Case description: This case report describes the successful treatment of a patient with high-grade parotid MEC and positive surgical margins using toripalimab plus cetuximab combined with radiotherapy, who achieved complete response one month after the completion of treatment. Conclusion: We report a case in which a patient with locally advanced high-grade parotid MEC with R2 resection achieved a complete response after postoperative adjuvant radiotherapy combined with toripalimab and cetuximab.