Aim: p53 is reportedly activated without any genotoxicity through redox modulation of redox factor 1 (REF1). REF1 is documented to modulate the redox status under selenomethionine (SeMet). In this study, we investigated the mechanism of p53 stabilization by SeMet. Materials and Methods: We mainly used ubiquitination assay and immunoprecipitation to determine the potential role of REF1 and c-jun N-terminal kinase 1 (JNK) in modulation of p53 stabilization by SeMet. Results: The amount of ubiquitinated p53 decreased significantly under SeMet treatment, suggesting that SeMet might inhibit the proteasome-dependent degradation of p53. In addition, we observed that JNK was considerably associated with p53 in REF1 siRNA-treated cells, implying a possible role for SeMet-induced REF1 activity in modulation of the interaction between JNK and p53 via changes in p53 redox status. Conclusion: Our results suggest that the alternate mechanism of p53 stabilization by SeMet might provide an important clue in elucidating the molecular mechanism of chemopreventative compounds against various oxidative stresses.