In this study, we validate tumor suppressor role of SNORD50A/B in p53 mutated (p53mt) breast cancers; however, we surprisingly find that it plays the complete opposite roles in p53 wild-type (p53wt) breast cancers, and demonstrate that SNORD50A/B induces p53 ubiquitination and degradation by mediating the interaction between TRIM21 and GMPS, thereby promoting the growth of p53wt breast cancers. Here, TRIM21 is linked to breast cancer.