Locally advanced operable oral squamous cell carcinoma (OSCC) continues to be a major therapeutic challenge despite the implementation of novel multi-modal treatment approaches. To improve local and local-regional control and to allow functional reconstruction after ablative surgery, neoadjuvant protocols have been developed during the last decade implementing radiochemotherapy prior to selective surgery. In the present retrospective analysis, the results of concurrent radiotherapy with 40 Gy and low-dose cisplatin-based chemotherapy followed by major surgery are presented for n=207 patients with an OSCC of stage III or IV. The overall survival for all patients analyzed was 49.5% after 60 months and 37.0% after 120 months. Further subgroup analysis found that histopathologic N0 tumours had a significantly better 5-year and 10-year overall survival rate than N+ tumours (p=0.004). In multivariate analysis, only postoperative N0 stage was a significant predictor for a favourable outcome (p=0.004). Overall disease-free survival of the whole patient collective was 70.4% after 60 months and 62.6% after 120 months with superior 60 month and 120 month disease-free survival for T0 (p=0.018) and N0 tumours (p=0.007), which was verified by multivariate analysis (p=0.019 and p=0.055, respectively). T+ tumours inherited a 2.5-fold increased risk for the development of local or loco-regional failure (p=0.05), and N+ tumours a 6.1-fold increased risk for the development of distant metastases (p<0.001). In conclusion, neoadjuvant radiochemotherapy with 40 Gy and concurrent low-dose cisplatin monotherapy followed by selective surgery is a feasible and reliable therapy concept, which results in encouraging overall and disease-free survival rates for therapy responders and which reliably selects therapy non-responders by the histopathological assessment of the neck dissection preparation. Those therapy non-responders might profit from intensified systemic therapy approaches.