In this study, we found that circHIPK3, upregulated by HIF-2α, could promote migration and invasion of HRGC cells via the miR-653-5p/miR-338-3p-NPR1 axis, indicating that circHIPK3 participated in metastatic promotion of GC under a long-term hypoxic microenvironment. This evidence concerns the gene NPR1 and gastric cancer.