Abstract: Objective To explore the expression of forkhead box C1 (FOXC1) gene in gastric cancer tissues and the effects of its silencing on the proliferation and apoptosis of human gastric cancer cells. Methods The expression of FOXC1 mRNA in 86 samples of gastric cancer tissues and adjacent normal tissues was detected by real-time fluorescent quantitative PCR. The relationship between the difference in FOXC1 mRNA expression and the clinicopathological characteristics of gastric cancer was analyzed. The expression of FOXC1 gene in gastric cancer cell line SGC7901 was silenced by siRNA technique. The effects of FOXC1 silencing on the proliferation and apoptosis were detected by MTT assay and flow cytometry. Results The expression of FOXC1 mRNA in gastric cancer tissues was significantly higher than that in adjacent normal tissues (P<0.05). The levels of FOXC1 mRNA in patients with tumors not shorter than 5 cm, at TNM stages Ⅲ-Ⅳ, with lymph node metastasis and distant metastasis were higher than those with tumors shorter than 5 cm, at TNM stages Ⅰ-Ⅱ, without lymph node metastasis or distant metastasis (P<0.05). After transfection, compared with the blank group, the level of FOXC1 mRNA significantly decreased in the siRNA-FOXC1 group (P<0.05). When treatment with 48 h and 72 h, compared with the blank group, the siRNA-FOXC1 group presented significantly decreased absorbance (P<0.05). Compared with the blank group, the siRNA-FOXC1 group showed remarkable decreases in the levels of proliferation-related proteins Ki67 and proliferating cell nuclear antigen (PCNA), B lymphoma-2 gene/Bcl-2 related X protein (Bcl-2/Bax), phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K and phosphorylated serine-threonine protein kinase (p-AKT)/AKT significantly (P<0.05), and increases in the apoptotic rate and the level of cleaved cysteinyl-aspartate specific protease 3 (cleaved caspase-3) (P<0.05). Conclusions FOXC1 is up-regulated in gastric cancer tissues, which is closely related to the clinicopathological characteristics of patients. After FOXC1 silencing, the proliferative ability of gastric cancer SGC7901 cells decreases but the apoptotic rate increases, which may be related to inhibiting the activation of the PI3K/AKT signal pathway.