Objective: To evaluate the value of two oral mucosal contouring methods for predicting acute radiation-induced oral mucositis (A-ROM) in nasopharyngeal carcinoma (NPC) patients. Methods: A total of 150 AJCC 7^th stage Ⅱ-IVB NPCs receiving radical tomotherapy (TOMO) in Zhejiang Cancer Hospital from 2017 to 2019 were included in this prospective observational study. Oral cavity contour (OCC) and mucosal surface contour (MSC) were applied to delineate the oral mucosal structure. A-ROM grade was prospectively assessed and recorded weekly according to RTOG scoring criteria. The prediction value of two methods for A-ROM was statistically compared. Results: The incidence rate of ≥3 grade A-ROM was 33.3%. In univariate analysis, V₅, V₁₀, V₁₅, V₄₅, V₅₀, V₅₅, V₆₀, V₆₅ and V₇₀ of OCC and V₅, V₁₀, V₅₀, V₅₅, V₆₀, V₆₅, V₇₀ and D_mean of MSC were significantly correlated with the risk of ≥3 grade A-ROM (all P<0.05). In binary logistic regression analysis, gender and smoking were significantly associated with the incidence of ≥3 grade A-ROM by using OCC (male vs. female: OR=0.141, 95%CI=0.037-0.538, P=0.004; smoking vs.non-smoking: OR=5.109, 95%CI=1.413-18.470, P=0.013). For MSC, gender, smoking, N stage and MSC- V₅₅ were the independent predictors (male vs. female: OR=0.129, 95%CI=0.032-0.519, P=0.004; smoking vs.non-smoking: OR=4.448, 95%CI=1.224-16.164, P=0.023; N stage: OR=2.291, 95%CI=1.268-4.137, P=0.006; MSC-V₅₅: OR=1.432, 95%CI=1.008-2.033, P=0.045). The cutoff value of MSC-V₅₅ was 7.70%, the area under ROC curve was 0.754, the sensitivity and specificity were 0.680 and 0.740, retrospectively (all P<0.001). Conclusions Compared with OCC, MSC yields a higher prediction accuracy for the severity of A-ROM in nasopharyngeal carcinoma patients receiving TOMO treatment.