The primary treatment for advanced-stage (stage III-IV) hypopharyngeal squamous cell carcinoma (HP SCC) include primary surgery followed by either adjuvant radiotherapy (RT) or adjuvant chemo-radiotherapy (CCRT) or definitive CCRT. However, the optimal primary treatment for advanced HP SCC remains controversial. We performed a retrospective analysis of newly diagnosed patients with stage III, IVA and IVB HP SCC at our institutions between September 2002 and September 2013. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional recurrence rate (LRR) and distant-metastasis rate (DMR) were analyzed and compared between primary surgery and definitive CCRT groups. We enrolled 367 consecutive patients in this retrospective study, 110 of whom did not meet study criteria. Among the 257 included patients, 124 patients was treated by primary surgery (SX group) and 133 patients was treated by definitive CCRT (CCRT group). With a median follow-up time of 5.83 years for the surviving patients, the five-year OS (53% vs 32%, P < 0.001), DFS (48% vs 28%, P < 0.001) were significantly higher in the SX group as compared with the CCRT group. The 5-year LRR (28% for SX group vs 53% for CCRT group, P < 0.001) was significantly lower in the SX group. Whereas, the 5-year distant metastasis rates (21% for SX group vs 25% for CCRT group, P = 0.276) were comparable between these 2 groups. Multivariate Cox regression analysis showed that primary treatment with surgery improved OS (hazard ratio [HR], 0.52; 95% CI, 0.33-0.82; P = 0.004), DFS (HR, 0.49; 95% CI, 0.32-0.75; P = 0.001) and decreased LRR (hazard ratio [HR], 0.34; 95% CI, 0.20-0.58; P < 0.001). By subgroup analysis, 24 patients with stage III & IVA diseases and achieving complete or partial response to induction chemotherapy in the CCRT group, the five-year OS (54% vs. 45%, P = 0.595), DFS (48% vs. 44%, P = 0.524), LRR (28.6% vs 27.4%, P = 0.909) and DMR (20.2% vs 18.0%, P = 0.753) are comparable to the SX group. Among patients with advanced stage HP SCC (stage III, IVA and IVB), primary radical surgery have significant better overall, disease-free survivals and loco-regional control rates than primary CCRT. Patients with stage III and IVA HP SCC, showing complete or partial response to induction chemotherapy, treated by primary CCRT have equivalent outcomes as compared to primary surgery. However, due to limited sample size, further large prospective study is still needed to identify patients with advanced hypopharyngeal cancer suitable for primary CCRT or organ preservation treatment.