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Background: The transcription factor FOXM1 is an important regulator of the cell cycle through controlling periodic gene expression during the G2 and M phases. One key target for FOXM1 is the gene encoding the protein kinase PLK1 and PLK1 itself acts in a positive feedback loop to phosphorylate and activate FOXM1. Both FOXM1 and PLK1 have been shown to be overexpressed in a variety of different tumour types. Methods: We have used a combination of RT–PCR, western blotting, tissue microarrays and metadata analysis of microarray data to study whether the FOXM1-PLK1 regulatory axis is upregulated and operational in oesophageal adenocarcinoma. Results: FOXM1 and PLK1 are expressed in oesophageal adenocarcinoma-derived cell lines and demonstrate cross-regulatory interactions. Importantly, we also demonstrate the concomitant overexpression of FOXM1 and PLK1 in a large proportion of oesophageal adenocarcinoma samples. This co-association was extended to the additional FOXM1 target genes CCNB1, AURKB and CKS1. In a cohort of patients who subsequently underwent surgery, the expression of several FOXM1 target genes was prognostic for overall survival. Conclusions: FOXM1 and its target gene PLK1 are commonly overexpressed in oesophageal adenocarcinomas and this association can be extended to other FOXM1 target genes, providing potentially important biomarkers for predicting post-surgery disease survival.