Soybean, an important leguminous crop valued for its high protein and oil content, obtains most of its nitrogen through symbiotic fixation processes. The symbiosis between soybeans and rhizobium can provide sufficient nitrogen for soybean growth. However, the signaling pathways underlying the establishment of the symbiosis are not so clear, especially the rhizobial type III effector-induced host response. In this study, we found that the single mutant HH103 nopAA::kan significantly affected the nodule number in soybeans. To further demonstrate the NopAA-triggered response in soybeans. Initial quantitative real-time PCR (qRT-PCR) tests showed that NopAA affects the expression of the soybean gene GmERF5, which was significantly upregulated upon inoculation with HH103 nopAA::kan, acting as a positive regulator of nodulation. The direct interaction between NopAA and GmERF5 was confirmed through yeast-two hybrid analysis. Furthermore, overexpression of GmERF5 in hairy roots indicated that GmERF5 may underlie the nodule phenotype of soybeans in response to NopAA. These findings provide new insights into the mechanisms by which soybean genes respond to rhizobial type III effectors to regulate symbiosis.