This study aims to study the effects of CXC motif chemokine ligand 8 (CXCL8)/ CXC chemokine receptor 1 (CXCR1) on the proliferation, apoptosis, invasion, and migration of human esophageal cancer cell ECA109 in vitro, and to explore the relationship between CXCL8/CXCR1 and forkhead box S1 (FOXS1) protein. The human esophageal cancer cells ECA109 were divided into control group, CXCL8 group, CXCL8+Con-siRNA group, and CXCL8+CXCR1-siRNA group after cell transfection. The final concentration of CXCL8 in each group was 10 μg/mL. MTT assay was used to detect cell proliferation; cloning assay was used to detect clone formation and flow cytometry was used to measure cell apoptosis. The invasion and migration of the cells were evaluated by Transwell assay and scratch assay, respectively. In addition, the protein levels of CXCR1 and FOXS1 were detected by Western blotting. The results showed that, compared to cells in the control group, CXCL8 significantly promoted the proliferation, cell cloning, invasion, and migration of ECA109 cells (P<0.05). However, this effect was blocked by CXCR1 interference (P<0.05). There were no significant differences in cell apoptosis in the CXCL8 group when compared to either the CXCL8+Con-siRNA group or the control group (P>0.05), whereas the cell apoptosis decreased significantly in CXCL8+CXCR1-siRNA group (P<0.05). Esophageal cancer cells in the CXCL8 group showed upregulated expression of CXCR1 and FOXS1 proteins compared to those in the control group (P<0.05). However, both CXCR1 and FOXS1 protein expressions were significantly decreased after interfering with CXCR1 (P<0.05). Altogether, the results suggest that CXCL8/CXCR1 promotes the proliferation, invasion, and migration of esophageal cancer cells in vitro, possibly by regulating FOXS1 protein expression.