Objective:To explore the mechanism of EYA1 (eyes absent 1) inhibiting the malignant progression of gastric cancer SGC7901 cells through regulating PTEN/PI3K/AKT signaling pathway. Methods: Twenty-nine pairs of gastric cancer tissues and para-cancerous tissues collected at the General Surgery center, Southwest Hospital Affiliated to Military Medical University during June 2016 and June 2018 were used in this study. Wb and RT-PCR assays were used to test the mRNA and protein expressions of EYA1 in gastric cancer tissues and the paired para-cancerous tissues; Transfection with plasmid or siRNAs were used to up-regulate or down-regulate EYA1 or PTEN expression in gastric cancer SGC-7901 cells; MTT, Flow Cytometry, Wound Healing and Transwell assays were carried out to detect cell proliferation, apoptosis, metastasis and invasion abilities, respectively. Results: EYA1 expression was decreased in gastric cancer tissues as compared with the para-cancerous tissues at both mRNA and protein levels (P<0.01); EYA1 over-expression significantly enhanced the proliferation, metastasis and invasion of SGC-7901 cells (all P<0.05), and inhibited cell apoptosis (P<0.05); moreover, its over-expressionsignificantly increased the expression of PTEN, and inhibited the activation of PI3K/AKT pathway (all P< 0.05 or P<0.01). However, the above effects mediated by EYA1 up-regulation were significantly impaired after the knockout of PTEN (all P<0.05 or P<0.01). Conclusion: EYA1 can inhibit the malignant progression of gastric cancer SGC-7901 cells through promoting the expression of PTEN and activating PI3K/AKT pathway.