The aim of the present study was to clarify the association of mTORC2 expression with the cancer progression and the anti-tumor effects of Torin-1 alone and combined treatment with Cetuximab in OSCC cells. The expressions of Rictor and SGK1 were immunohistochemically evaluated and the relationships between the expressions of molecular markers and clinicopathological factors were determined. Moreover, OSCC cells were treated with Torin-1, Cetuximab or combined agents, and anti-tumor effects of OSCC cells were examined in vitro and in vivo. Rictor and SGK1 expressions were significantly associated with tumor stage and pattern of invasion in OSCC sections (P<0.05 and P<0.01, respectively). Treatment of OSCC cell lines with Torin-1 resulted in dose and time-dependent inhibition of proliferation with decrease of phosphorylation on downstream molecules. Combined treatment with Torin-1 and Cetuximab resulted in enhanced anti-tumor effects in vitro compared with either agent alone. Furthermore, treatment of mice bearing OSCC xenografts with Torin-1 and Cetuximab also demonstrated a remarked growth inhibition of tumor volumes. The results suggested that new regimens of systemic therapy combined with Cetuximab and Torin-1 may be useful for very advanced OSCC patients.