Background Gastric cancer (GC) is a common and grievous disorder with high heterogeneity. Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1), a pseudophosphatase without catalytic activity, plays a important roles in cellular pathways and various cancers. However, its role and mechanism in GC remain unclear. Objectives This study aimed to explore the role and possible mechanism of STYXL1 in GC cells. Results The results showed that STYXL1 expression was elevated in GC. Both loss- and gain-of-function results showed that STYXL1 enhanced cell viability, colony formation, cell invasion and migration, and the protein expression of BCL-2 and Vimentin, but reduced the apoptosis rate and the protein level of BAX, cleaved caspase 3 and E-Cadherin in vitro. Mechanically, the levels of p-PI3K/PI3K and p-AKT/AKT were observably elevated by overexpression of STYXL1, and markedly reduced by silencing of STYXL1 in both SNU-1 and HGC-27 cells. Conclusion STYXL1 promoted cell growth, migration, invasion and EMT with decreased apoptosis, which was closely related with the activation of PI3K/AKT pathway in GC.