To analyze the survival rates and quality of life of human papillomaviruse (HPV)-negative patients with advanced oropharyngeal cancer after different combined treatments with chemotherapy, surgery and radiotherapy. We retrospectively analyzed the data of patients with oropharyngeal cancer hospitalized in our hospital from January, 2015 to December, 2020, and after case analysis of the clinical, imaging and pathological data, 405 patients were included in this study and grouped according to the treatments they received. Kaplan-Meier and Log-rank analysis were used to calculate the overall survival rate and the survival rate of patients with different treatments. The self-rated quality of life of the tumor-free survivors was assessed using UW-QOL (4) questionnaire and compared among the patients with different treatments. Among the 405 patients included in this study, 146 received treatments with chemotherapy+surgery+radiotherapy (CSRT), 138 received surgery+radiotherapy (SRT) and 121 were treated with radiotherapy+chemotherapy (RCT). The overall survival rates of the 3 groups at 1, 3 and 5 years were 85.1%, 67.1% and 56.9%, respectively, and the survival rates of patients receiving CSRT, SRT and RCT did not differ significantly (P > 0.05). A total of 280 UW-QOL (4) questionnaires were distributed and 202 (72.14%) were retrieved. The average total scores decreased in the order of CSRT > SRT > RCT; the scores were significantly higher in CSRT group than in SRT and RCT (P < 0.05), but did not differ significantly between SRT and RCT groups (P > 0.05). CSRT, SRT and RCT are all treatment options for locally advanced oropharyngeal cancer, but CSRT may achieve better quality of life of the patients than SRT and RCT.