Here, we report that dasatinib has anti‐growth, anti‐angiogenic and pro‐apoptotic effects on both YD‐38 (non‐tumorigenic) and HSC‐3 (tumorigenic) human oral cancer cells, and these effects are mediated through control of the expression and phosphorylation of multiple targets including Src, EGFR, STAT‐3, STAT‐5, PKB, ERK‐1/2, S6, eIF‐2α, GRP78, caspase‐9/3, Mcl‐1 and HIF‐1α. Here, HSPA5 is linked to lip and oral cavity carcinoma.