Aberrant expression of the SRY-related HMG-box (SOX) genes contributes to tumor development and progression. This research aimed to identify the regulation of the SOX genes in stomach adenocarcinoma (STAD). Expression profiles downloaded from The Cancer Genome Atlas (TCGA) were conducted to analyze the expression and function of the SOX genes. A competing endogenous RNAs (ceRNA) network mediated by the SOX genes was effectively constructed consisting of 64 lncRNAs, 29 miRNAs, and 11 SOX genes based on predicted miRNAs shared by lncRNAs and mRNAs using miRDB, TargetScan, miRTarBase, miRcode, and starBase v2.0. SOX9 was identified as a prognostic signature, which showed the usefulness of diagnosis and prognosis of STAD by the receiver operating characteristic (ROC) and Kaplan-Meier curves. SOX9 was also shown specifically in STAD and identified as highly expressed in the gastrointestinal tract. Gene Ontology (GO) enrichment analysis showed that SOX9 might influence the genes related to the pattern specification process, sodium ion homeostasis, and potassium ion transport, mainly including FEZF1, HOXC13, HOXC10, HOXC9, HOXA11, DPP6, ATP4B, CASQ2, KCNA1, ATP4A, and SFRP1. Furthermore, HOTAIR knockdown, miR-206-mimic transfection, the Cell Count Kit-8 (CCK-8) assay were performed to verify the function of HOTAIR/miR-206/SOX9 axis, which was identified in the ceRNA network analysis. HOTAIR could induce proliferation potentially by competitively binding miR-206/SOX9 axis in STAD. These findings provide new clues with prognostic and therapeutic implications in STAD and suggest that HOTAIR/miR-206/SOX9 might be a potential new strategy for therapeutic targeting of gastric cancer.