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Cadmium is not only seriously harmful to the growth and development of plants but threatens human health through the food chain. E3 ubiquitin ligase genes have been studied widely; however, whether it mediates cadmium stress in plants remains unclear. In this report, we provided evidence on the response of a U-box E3 ubiquitin ligase gene SlUPS to cadmium stress. The full-length CDS of SlUPS was 873 bp, with 223 amino acid residues. SlUPS was sufficiently induced by cadmium in leaf and root tissues. The expression of the SlUPS gene reached the maximum in leaves and roots in 3 and 9 h during CdCl2 treatment. The gene expression increased with progressively increasing concentrations of cadmium. The viability of yeast carrying pYES2-SlUPS, with SlUPS overexpressed, was higher than that in the control group. The transgenic Arabidopsis plants that overexpressed SlUPS showed a significantly higher germination rate and better growth than the control plants during the cadmium treatment. In summary, our study showed that SlUPS might positively regulate the plant response to cadmium stress. These results provided insights facilitating further investigations into the roles of U-box E3 ubiquitin ligase genes in heavy metal stress.