PurposeTo identify whether p16 status or response to induction chemotherapy (IC) predicts the radiotherapy (RT) response and survival outcomes in Chinese oropharyngeal squamous cell carcinoma (OPSCC). MethodsA total of 211 patients, including 128 p16-positive and 83 p16-negative were analyzed. All patients underwent IC followed by definitive RT or concurrent chemoradiotherapy (CCRT). Propensity score matching (PSM) was used to eliminate the baseline variations. ResultsAge, sex, smoking history, alcohol history, and primary site were unbalanced between different p16 status subgroups. Before PSM, the objective response rates to IC between p16-positive and p16-negative groups were 80.5 % and 85.5 % (p = 0.344). After RT, the complete response (CR) rates were 73.4 % and 66.3 %, respectively (p = 0.264). IC-sensitive (IC-s) subgroups had a higher percentage of RT-CR rate than the IC-resistant (IC-r) subgroups in both p16-positive and p16-negative patients. IC-s showed significant improvement in cancer-specific survival (CSS) (92.9 % vs. 53.6 %, p < 0.0001), progression-free survival (PFS) (p < 0.0001), locoregional relapse-free survival (LRFS) (p < 0.0001) and distant metastasis-free survival (DMFS) (p = 0.025). After PSM, the CR rates among different p16 groups remained comparable following RT (71.2 % vs. 65.8 %, p = 0.476). Before or after PSM, CSS, PFS, LRFS, and DMFS were similar between different p16 status either in IC-s or IC-r subgroups (p > 0.05). IC-r was independently associated with shorter PFS (HR = 2.661, p = 0.002) and LRFS (HR = 2.876, p = 0.002; HR = 2.78, p = 0.018). ConclusionsResponse to IC is an important predictor of prognosis in Chinese OPSCC treated with definitive RT. Poor response to IC is associated with unsatisfactory outcomes either in p16-positive or p16-negative OPSCC.