Gastric cancer (GC), which features high prevalence and mortality rate, remains the third most lethal cancer worldwide. The paper was designed to explore the impacts of collagen type IV alpha 1 (COL4A1) on GC, along with its potential mechanism. The mRNA and protein expressions of COL4A1 in GC cells were assessed using RT-qPCR and Western blot. After depleting COL4A1, RT-qPCR and Western blot were conducted again to check the transfection efficacy. With the application of CCK-8, wound healing and transwell, the capabilities of cells to proliferate, migrate and invade were appraised, respectively. Moreover, Western blot tested the protein levels of factors involved in migration, proliferation, epithelial-mesenchymal transition (EMT) and Hedgehog signaling. As a result, COL4A1 displayed elevated expression in GC tissues and cells, while its knockdown inhibited the cell viability, migration, invasion and EMT in GC. According to Gene Set Enrichment Analysis (GSEA), COL4A1 was involved in the regulation of Hedgehog signaling pathway, which was then further verified by the detection of Hedgehog-related proteins. To figure out the relationship between COL4A1 and Hedgehog signaling pathway, we used purmorphamine, an agonist of Hedgehog, to treat GC cells, finding that COL4A1 blocked Hedgehog signaling to inhibit the aggressive phenotypes of GC cells. In short, COL4A1 silence was testified to exhibit suppressive effects on the malignant process of GC, suggesting that COL4A1 might be a potent hallmark of GC therapy.