We found that ANXA1 regulated SQSTM1 expression through autophagy, ANXA1 inhibited BECN1 and ATG5-dependent autophagy by PI3K/AKT signaling activation in the NPC cells, and ANXA1-suppressed autophagy promoted NPC cell in vitro migration and invasion and in vivo metastasis. Here, SQSTM1 is linked to nasopharyngeal carcinoma.