ackground: Autophagy has a paradoxical role in cancer. Autophagy-related 16-like 1 (ATG16L1) and the light chain 3 B (LC3B) are proteins that form an essential part of the membranes of the autophagosomes. To date, the significance of ATG16L and LC3B expression in OSCC has not been fully clarified. Aim: Aim of the current study was to investigate ATG16L and LC3B tissue protein expression levels in tissues which were taken from OSCC patients then correlate our results with pathological and clinical patients’ data. Methods: ATG16L and LC3B expression was assessed in 40 patients with OSCC using immunohistochemistry. We followed the patients for 5 years for progression and recurrence of the disease and for survival. Results: High ATG16L1 and LC3B expression was correlated with higher grade (p=0.021 and 0.049, respectively), advanced stage of the tumor (p=0.003 and 0.005, respectively), presence of lymph node metastases (p=0.007 and 0.033, respectively), distant metastases (p=0.045 and 0.040, respectively), poor response to therapy (p=0.018 and 0.050, respectively), higher incidence of tumor recurrence, worse 5 year DFS and OS rates (p<0.001). Conclusion: ATG16L and LC3B overexpression are markers of poor prognosis in OSCC patients.