Collectively, our data provide evidence to show that FOXM1 regulates TYMS to modulate 5-FU sensitivity in CCA cells and that the high FOXM1 expression confers 5-FU resistance in most of these CCA cells through promoting high levels of TYMS expression (e.g., in KKU-M213, KKU-M214 and KKU-D131 cells). Here, FOXM1 is linked to cholangiocarcinoma.