This study aimed to investigate whether the genetic variants of CRTC1, BARX1, FOXP1 and FOXF1 are associated with the development of oesophageal adenocarcinoma (OA) in Chinese population. A total of 744 OA patients and 1138 controls were included in this study. Here we genotyped four SNPs, rs10419226 of CRTC1, rs11789015 of BARX1, rs2687201 of FOXP1 and rs3111601 of FOXF1. The chi-square test was used to compare the genotype and allele frequencies between the patients and controls. The student’s t-test was used to compare FOXP1 expression in the tumour and the adjacent normal tissues. The relationship between genotypes of rs2687201 and FOXP1 expression was investigated by one-way analysis of variance test. Patients were found to have significantly higher frequency of allele A of rs2687201 and allele C of rs3111601 when compared with the controls (49.2 vs 43.4%, P=0.0008 for rs2687201; 29.1 vs 24.0%, P=0.0003 for rs3111601). There was a significantly higher expression level of FOXP1 in the tumour than in the adjacent normal tissue (0.0052 ± 0.0021 vs 0.0027 ± 0.0018, P <0.001). Patients with genotype AA were found to have remarkably higher FOXP1 expression in the tumour than those with genotype CC ( P=0.01). To conclude, the varients of FOXP1 and FOXF1 genes are functionally associated with OA in Chinese population. With the identification of more susceptible loci, the combined effect of these markers may be helpful for the surveillance of OA.