The mechanism of extracellular matrix induced tumor progression is poorly understood. Based on the TCGA database and clinical tumor tissues analysis, we observed abundant type I collagen expression in tumor tissues and poor overall survival in gastric patients with high integrin 131 (ITGB1) expression. In vitro, our study found that 3D collagen culture promoted the capability of colony formation and growth in ITGB1 positive gastric cancer, whereas limited colony growth was observed in ITGB1 negative gastric cancer, suggesting the role of ITGB1 in type I collagen associated tumor progression. Mechanistically, we demonstrated that type I collagen was capable of promoting the activation of BCL9L/beta-catenin signaling pathway through ITGB1, thereby contributing to the gastric cancer development. Subsequently, beta-catenin signals further up-regulated the expression anti-apoptosis protein BCL2, leading to the chemo-resistance in gastric cancer cells. Blockade of 13-catenin signals efficiently improved the anticancer effects of chemotherapy, providing an innovative sight for clinical gastric cancer therapy.