Alkylresorcinols are phenolic lipids that mainly exist in the cortex of grains, and they exhibit anticancer activity against various cancer cells in vitro. However, the underlying action mechanisms are still unclear. In our study, the influence of alkylresorcinols C19:0 and C21:0 (ARs) upon migration, invasion, and autophagy in human hepatoblastoma HepG2 cells was evaluated. Results showed that ARs at 80 and 160 µg/mL significantly suppressed cells proliferation, migration, and invasion, downregulated the expression of proteins RhoA and MMP‐7 associated with migration and invasion. ARs at 160 µg/mL, the rate of LC3 puncta was appreciably increased. After autophagy was blocked by 3‐MA or CQ, the expression of LC3II was significantly increased in 3‐MA+ARs group and p62 was significantly decreased in CQ+ARs group. The results indicate that ARs may promote autophagic flow. ARs (80, 160 µg/mL) significantly inhibited the expression of proteins p‐mTOR, p‐PI3K, and p‐Akt related to the PI3K/Akt pathway. The results of the present study suggest that ARs can activate autophagy and suppresses the biological behaviors of HepG2 cells by inhibiting the activation of MMP‐7, Rho/Rho‐associated protein kinase, and activation of the phosphatidylinositol 3‐kinase/Akt signaling pathway. Practical Application The anticancer mechanism of ARs in wheat bran was studied, which provided a basis for the development of anticancer functional auxiliary food with wheat bran as raw material. It is of great practical significance to promote the effective utilization of grain processing by‐products and improve the economic benefits of the grain industry.