Overall, we determined that AA treatment resulted in an increase in Grp78 expression and associated enhancement of IRE1α and JNK phosphorylation in tongue cancer cells, indicating that AA induces the apoptotic death of these tumor cells via the activation of the ER Grp78/IRE1α/JNK signaling pathway.Although we found that AA induced ER stress and activated the Grp78/IRE1α/JNK and Calpain pathways to inhibit tongue cancer growth. This evidence concerns the gene ERN1 and tongue cancer.