It's frequently stated that the pyruvate kinase M2 (PKM2) and Warburg effect are important for cancer development by accumulating more raw materials for macromolecule biosynthesis. However, the correlation between PKM2 and cancer is poorly reported. Here, we investigated the PKM2 expression in esophageal squamous cell cancer (ESCC). We observed that the expression of PKM2 was much higher in ESCC than in control normal tissue, and it is highly associated with many clinical features and prognosis. Specially, we found that the expression of PKM2 was closely related to the differentiation state of ESCC, and we further confirmed this discovery in vitro. As a result, out data indicated that PKM2 might be a useful indicator for determining the survival of patients with ESCC. Considering previous researches on the link among PKM2, Warburg effect, and differentiation, our study inferred the direct roles of PKM2 and Warburg effect in the differentiation of cancer cells rather than only providing synthetic intermediates for the promotion of cancer's progression.