NFE2L3 knockdown significantly inhibited the growth of cancer cells; NFE2L3 overexpression increased 20S proteasome activity via increase POMP; NFE2L3 overexpression decreases Rb and p53 protein through ubiquitin-dependent degradation; Overexpression of NFE2L3 induced tumor growth and hepatic metastasis. Here, NFE2L3 is linked to cancer.