Abstract Objective As one broader class of non-coding RNAs (lncRNAs), non-coding antisense (AS) transcripts are functionally characterized to play pivotal roles in various pathophysiological processes, including tumor biology. Methods In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined. Results The expression of GAS6-AS1 was markedly upregulated in GC tissues and is associated with advanced stage (III + IV) of GC patients. Gain-of-function and loss-of-function experiments showed that GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and xenograft tumor growth in vivo by promoting entry into S-phase. The mechanistic investigations showed that GAS6-AS1 can control the expression of its cognate sense gene GAS6 at the transcriptional or translational levels by forming a RNA-RNA duplex, consequently inducing an increase of AXL level and driveling AXL signaling pathway activation. Conclusions Taken together, our studies indicate that GAS6-AS1 significantly driving the aggressive phenotype in GC through activating its cognate sense gene GAS6 , and provides a more complete understanding of GAS6-AS1 as a potential therapeutic target for GC. Highlights • GAS6-AS1 was markedly upregulated in gastric cancer (GC). • GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and in vivo. • GAS6-AS1 can control GAS6 level by forming a RNA-RNA duplex in GC. • GAS6-AS1 may be as a potential GC biomarker. [ABSTRACT FROM AUTHOR]