In this study, the role of E3 ubiquitin ligase GmSNE3 in halosulfuron methyl (HSM) inhibiting soybean nodulation was investigated. was strongly induced by HSM stress, and the overexpression of significantly reduced the number of soybean nodules. Further investigation found that GmSNE3 could interact with a nodulation signaling pathway 1 protein (GmNSP1a) and GmSNE3 could mediate the degradation of GmNSP1a. Importantly, GmSNE3-mediated degradation of GmNSP1a could be promoted by HSM stress. Moreover, HSM stress and the overexpression of GmSNE3 resulted in a substantial decrease in the expression of the downstream target genes of . These results revealed that HSM promotes the ubiquitin-mediated degradation of GmNSP1a by inducing GmSNE3, thereby inhibiting the regulatory effect of on its downstream target genes and ultimately leading to a reduction in nodulation. Our findings will promote a better understanding of the toxic mechanism of herbicides on the symbiotic nodulation between legumes and rhizobia.