Objective This study aims to explore the application value of serum CA19-9, SCC, and CEA as biomarkers in the short-term efficacy assessment of patients with advanced sinus tumors following radiochemotherapy, to provide more precise biomarkers for predicting short-term treatment response.Methods This retrospective study included 120 patients with advanced sinus tumors treated at The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology from January 2021 to January 2024. All patients received conformal intensity-modulated radiotherapy combined with nab-paclitaxel (Nab-P) and nedaplatin (NDP) chemotherapy. Based on the clinical response after treatment, patients were divided into a remission group (64 patients) and a non-remission group (56 patients). The serum levels of CA19-9, SCC, and CEA before and after treatment were compared between the two groups. Spearman correlation analysis was used to evaluate the relationship between the levels of serum CA19-9, SCC, CEA, and the clinical remission status of patients with advanced sinus tumors. Logistic regression analysis was conducted to determine the factors affecting the efficacy of radiochemotherapy in patients with advanced sinus tumors. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of serum CA19-9, SCC, and CEA levels for prognosis.Results The pre-to-post-treatment changes (decreases) in serum CA19-9, SCC, and CEA levels in the remission group were significantly greater than those in the non-remission group (P < 0.05). Serum CA19-9, SCC and CEA levels were positively correlated with clinical non-remission (r_s = 0.377, 0.528, 0.619, P < 0.05). Logistic regression analysis showed that squamous cell carcinoma pathological type [O^R = 7.023 (95% CI: 1.630, 30.248) ], positive surgical margin [O^R = 11.133 (95% CI: 1.997, 62.065) ], positive cervical lymph nodes [O^R = 11.474 (95% CI: 2.362, 55.739) ], high CA19-9 level [O^R = 1.069 (95% CI: 1.004, 1.138) ], high SCC level [O^R = 4.751 (95% CI: 2.081, 10.847) ] and high CEA level [O^R = 1.722 (95% CI: 1.253, 2.368) ] were all risk factors for non-remission after chemoradiotherapy in patients with advanced sinus tumors (P < 0.05). ROC curve analysis showed that serum CA19-9 had a sensitivity of 57.10% (95% CI: 0.432, 0.703) and a specificity of 79.70% (95% CI: 0.678, 0.887); serum SCC had a sensitivity of 64.30% (95% CI: 0.504, 0.767) and a specificity of 84.40% (95% CI: 0.731, 0.922); serum CEA had a sensitivity of 71.40% (95% CI: 0.578, 0.827) and a specificity of 87.50% (95% CI: 0.769, 0.945). The combined detection of the three markers showed a sensitivity of 80.40% (95% CI: 0.676, 0.898) and a specificity of 92.20% (95% CI: 0.827, 0.974).Conclusion Serum CA19-9, SCC and CEA levels can be used as effective biomarkers for evaluating the efficacy of chemoradiotherapy in patients with advanced sinus tumors. The combined detection of the three can improve the sensitivity and specificity of predicting the efficacy of chemoradiotherapy in patients with advanced sinus tumors.