RNF122 is a novel gene which can inhibit cellular growth and induce apoptosis. RNF122 contains a RING-H2 domain. RING domain mutant was constructed to explore the relationship between RING domain and apoptosis. MTT and apoptosis experiments revealed that RNF122 closely related to cell viability dependent on its RING domain. Further exploration implied that RNF122 can negatively regulate ERK pathway, whereas RING domain mutant RNF122 can enhance the phosphorylation of ERK. It can be concluded that RNF122 may regulate cellular viability through ERK pathway. In short, RING domain is critical to the function of RNF122.