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Background UXT is highly expressed in tumor tissues, which function as a vital role in tumor progression. However, the exact role and potential mechanism of UXT in the tumorigenesis of breast cancer remains largely unknown. Methods Expression patterns of UXT and MEG3 were examined using qRT-PCR and western blot, respectively. The capacity of cell proliferation, apoptosis, migration and invasion was assessed using CCK-8, flow cytometry and transwell assays. The methylation of MEG3 promoter was determined using methylation specific PCR. Co-immunoprecipitation was performed to measure the UXT/DNMT3b interaction. RNA-immunoprecipitation was subjected to evaluate the regulation of MEG3 on p53 activity. The xenograft tumor experiment was further conducted to certify the molecular mechanism. Results UXT was up-regulated while MEG3 was down-regulated in breast cancer tissues and cell lines. UXT knockdown or MEG3 overexpression significantly inhibited the proliferation, promoted the apoptosis, and weakened the migration and invasion of MCF7 and ZR75 cells. The hypermethylation of MEG3 promoter was found in breast cancer cells, which was modulated by highly expressed DNMT3b. UXT inhibited the level of MEG3 via recruiting DNMT3b to its promoter. Mechanistically, MEG3 positively regulated the transcriptional activity of p53 via binding with it, thus regulating cell apoptosis, migration and invasion. The xenograft tumor experiment indicated that UXT negatively regulated the MEG3/p53 axis in a DNMT3b-dependent manner to promote the tumor growth. Conclusions UXT, a novel DNMT3b-binding protein, aggravates the progression of breast cancer through MEG3/p53 axis, which may provide a new insight involving in the treatment of breast cancer.