Laminin subunit alpha-5 (LAMA5) has been identified as an oncogene in many cancers, while its role and mechanism in gastric cancer (GC) remain to be explored. Here, the influences of LAMA5 knockdown on GC were investigated in vitro and in vivo. LAMA5 expression was silenced in GC cells alone or in combination with the signal transducer and activator of transcription 3 (STAT3) activator Colivelin, followed by CCK-8, colony formation, EdU, flow cytometry, wound healing assay, and Transwell assay. The regulatory relationship between Myc-associated zinc finger protein (MAZ) and LAMA5 was characterized by ChIP and luciferase reporter analysis. The effect of knockdown of MAZ alone or in combination with LAMA5 overexpression on GC was investigated in vitro and in vivo. LAMA5 was highly expressed in GC cells, and knockdown of LAMA5 inhibited GC cell malignant aggressiveness, which was reversed by the Colivelin treatment. The transcription factor MAZ bound to the promoter of LAMA5 to activate its transcription, and the anti-tumor effects of sh-MAZ on GC cells in vitro and in vivo were overturned by LAMA5 overexpression. In conclusion, MAZ promotes GC cell proliferation and migration by the LAMA5/STAT3 axis, implying that this axis can function as a target for GC therapy.