Increasing evidence indicates that long noncoding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level and the function of SPRY4-IT1 in the progression of gastric cancer (GC) have been rarely reported. Here we found that SPRY4-IT1 was upregulated in GC. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited GC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell growth. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion. Bioinformatics analysis predicted that there is a SPRY4-IT1/miR-101-3p/AMPK axis in GC progression. A dual-luciferase reporter system validated the direct interaction of SPRY4-IT1, miR-101-3p, and AMPK. Western blot verified that the inhibition of SPRY4-IT1 decreased AMPK expression. Furthermore, silencing SPRY4-IT1 suppressed GC growth in vivo. Importantly, we demonstrated that SPRY4-IT1 was upregulated in serum exosomes from GC patients and correlated with cancer metastasis. Altogether, silencing SPRY4-IT1 suppresses the progression of GC by interacting with miR-101-3p and decreasing inhibiting AMPK expression. Taken together, our study demonstrates that SPRY4-IT1 could act as a potential therapeutic target for GC patients.