Oral squamous cell carcinoma (OSCC) is the fifth common cause of cancer mortality in Taiwan with high incidence and recurrence and needs new therapeutic strategies. In this study, ursolic acid (UA), a triterpenoid, was examined the antitumor potency in OSCC cells. Our results showed that UA inhibited the proliferation of OSCC cells in a doseâ and timeâdependent manner in both Ca922 and SCC2095 oral cancer cells. UA induced caspaseâdependent apoptosis accompanied with the modulation of various biological biomarkers including downregulating Akt/mTOR/NFâÎșB signaling, ERK, and p38. In addition, UA inhibited angiogenesis as evidenced by abrogation of migration/invasion and blocking MMPâ2 secretion in Ca922 cells. Interestingly, UA induced autophagy in OSCC cells, as manifested by LC3BâII conversion and increased p62 expression and accumulation of autophagosomes. Inhibition by autophagy inhibitor enhanced UAâmediated apoptosis in Ca922 cells. The experiment provides a rationale for using triterpenoid in the treatment of OSCC.