Autophagy is a cell survival mechanism that works for the survival of cells under various physiological and pathological conditions. ATG5 is a key protein in the process of autophagy propagation and is involved in tumor development and progression. Chemotherapeutic agents targeting ATG5 enhance the host's immune response in various human cancers and intensify the effectiveness of chemotherapy. However, the physiological role of ATG5 protein in oral squamous cell carcinoma (OSCC) has not been fully recognized. The purpose of this study was to examine the correlation between clinico-pathological factors of OSCC patients and ATG5 immunoexpression through immunohistochemistry (IHC) in the tissues of OSCC patients treated at our hospital, and to analyze the regarding influences and their mechanisms. The authors analyzed 20 OSCC patients from National University Dental Hospital, at Pusan National University from January 2002 to December 2007, which were eligible for the study. Data were obtained by reviewing the medical records of the OSCC patients, and ATG5 immunoexpression was obtained using IHC staining in the tissue samples of the OSCC patients. In the tissue sample of OSCC patients, the immunoexpression of ATG5 elevated, in comparison to the normal oral mucosa, and there was a significant correlation with Drinking, Pathological Stage. In regards to Cox regression analysis, Clinical stage, Tumor size, Histopathologic grade, Cervical nodal metastasis, Loco-regional recurrence, and ATG5 expression have statistically significant correlations. These results imply that the changes in the expression of ATG5 proteins in OSCC can be a prominent factor in the OSCC progression and the prognosis of OSCC patients.