Repeated administration of apatinib has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that had a low expression in GC, and homeobox gene C10 (), a carcinogenic gene, was highly expressed in GC, while the molecular mechanism of involved in apatinib resistance in GC cells is still unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of and in GC tissues or cell lines. The expression levels of associated proteins were detected by Western blot. Cell counting kit-8 (CCK-8), the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and flow cytometry assays were conducted to detect cell viability, proliferation, and apoptosis of MGC-803/AP and AGS/AP cells . The dual-luciferase reporter assay was used to verify the targeted relationship between miR-129-5p and . The xenograft model was established to examine the effect of , and the protein expression in tumor xenograft was assessed by immunohistochemistry. had a low expression in GC tissues and apatinib-resistant cell lines, while was highly expressed. Meanwhile, overexpression of and knockdown of could enhance the chemosensitivity of MGC-803/AP and AGS/AP cells. Dual-luciferase reporter assay confirmed targeted and downregulated its expression level. inhibited proliferation and promoted apoptosis of MGC-803/AP and AGS/AP cells by downregulating . The experiment also confirmed that reduced apatinib resistance in GC cells by targetedly inhibiting . was upregulated in GC tumor xenograft tissues. restrains apatinib-resistant of GC cells by regulating .