Objectives: To probe the action and mechanism of Safflower Polysaccharide (SPS) on Gastric Cancer (GC) cells. Materials and Methods: qRT-PCR detected miR-6738-3p expression levels. MTT assay and flow cytometry were adopted for the measurement of GC cell survival rate and apoptosis. ELISA analysis examined the levels of inflammatory factors. Results: miR-6738-3p was significantly decreased in GC cell lines, especially in AGS cells, relative to GES-1 cells. SPS treatment dose-dependently reduced the survival rate of AGS cells and induced cell apoptosis and inhibited inflammation. MiR-6738-3p overexpression also induced apoptosis enhancement and inflammation arrest in AGS cells. SPS increased miR-6738-3p content in AGS cells. Moreover, miR-6738-3p deletion reversed the functions mediated by SPS on AGS cell apoptosis promotion and inflammation suppression. Conclusion: Safflower polysaccharide promotes apoptosis and suppresses inflammatory reaction in GC cells by up-regulating miR-6738-3p.