〔Abstract〕 Objective To investigate the function and clinical significance of nuclear matrix binding region binding protein 1(SATB1) and epidermal growth factor receptor(EGFR) in gastric cancer. Methods The expression of SATB1 and EGFR was detected by immunohistochemistry in 60 cases of paraffin-embedded gastric cancer and 39 cases of gastric mucosal inflammation. Small interfering RNA(siRNA) was transfected into gastric cancer cells. The expression of SATB1 and EGFR after transfection was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR) and Western blot. The cell migration and invasion changes of MGC803 after transfection were detected by cell scratch test and Transwell test. The prognosis of gastric cancer patients with different SATB1 and EGFR expression was analyzed by KM survival analysis. Results The expression of SATB1 and EGFR in gastric cancer tissues was higher than that in gastric mucosa inflammation tissues, and the difference was statistically significant(P<0.05). The expression of SATB1 was correlated with lymph node metastasis and distant metastasis of gastric cancer, and the difference was statistically significant(P<0.05). EGFR expression was also associated with distant metastasis, and the difference was statistically significant(P<0.05). There was a positive correlation between the expression of SATB1 and EGFR in gastric cancer tissues(r=0.49,P<0.05). RT-qPCR and Western blot showed that siRNA could effectively knock down the expression of SATB1 and EGFR in gastric cancer cells. The results of cell scratch and Transwell experiments showed that the migration and invasion of gastric cancer cells were inhibited by knocking down SATB1 and EGFR. The results of KM survival curve showed that gastric cancer patients with low expression of SATB1 had a better prognosis, while those with low expression of EGFR had a better prognosis. Conclusion The expression levels of SATB1 and EGFR are closely related to lymph node metastasis and distant metastasis of gastric cancer, and decreasing the expression levels of SATB1 and EGFR can inhibit the migration and invasion of gastric cancer.