Oleic acid (OA), a main ingredient of Brucea javanica oil (BJO), is widely known to have anticancer effects in many tumors. In this study, we investigated the anticancer effect of OA and its mechanism in tongue squamous cell carcinoma (TSCC). We found that OA effectively inhibited TSCC cell proliferation in a dose- and time-dependent manner. OA treatment in TSCC significantly induced cell cycle G0/G1 arrest, increased the proportion of apoptotic cells, decreased the expression of CyclinD1 and Bcl-2, and increased the expression of p53 and cleaved caspase-3. OA also obviously induced the formation of autolysosomes and decreased the expression of p62 and the ratio of LC3 I/LC3 II. The expression of p-Akt, p-mTOR, p-S6K, p-4E-BP1 and p-ERK1/2 was significantly decreased in TSCC cells after treatment with OA. Moreover, tumor growth was significantly inhibited after OA treatment in a xenograft mouse model. The above results indicate that OA has a potent anticancer effect in TSCC by inducing apoptosis and autophagy via blocking the Akt/mTOR pathway. Thus, OA is a potential TSCC drug that is worthy of further research and development.