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Soluble solids content (SSC) is an important quality trait of wax gourd, but reports about its regulatory genes are scarce. In this study, the SSC regulatory gene <i>BhSSC2.1</i> in wax gourd was mined via quantitative trait locus (QTL) mapping based on high-density genetic mapping containing 12 linkage groups (LG) and bulked segregant analysis (BSA)-seq. QTL mapping and BSA-seq revealed for the first time that the SSC QTL (107.658–108.176 cM) of wax gourd was on Chr2 (LG2). The interpretable phenotypic variation rate and maximum LOD were 16.033% and 6.454, respectively. The QTL interval contained 13 genes. Real-time fluorescence quantitative expression analysis, functional annotation, and sequence analysis suggested that <i>Bch02G016960</i>, named <i>BhSSC2.1</i>, was a candidate regulatory gene of the SSC in wax gourd. Functional annotation of this gene showed that it codes for a NADP-dependent malic enzyme. According to <i>BhSSC2.1</i> sequence variation, an InDel marker was developed for molecular marker-assisted breeding of wax gourd. This study will lay the foundation for future studies regarding breeding and understanding genetic mechanisms of wax gourd.