The objectives of the present study are to explore role of pyruvate kinase isoenzyme type M2 (PKM2) in progression of Kazakh's esophageal squamous cell carcinoma (ESCC) in Xinjiang, China, and to clarify mechanism of PKM2 in malignant phenotype. PKM2 expression was examined using immunohistochemistry (IHC) in 101 matched pairs of ESCC and normal adjacent tissues (NATs) and using enzyme-linked immunosorbent assay (ELISA) in 35 serum samples of Kazakh's ESCC and 8 serum samples of healthy subjects. To investigate mechanism, small interfering RNA (siRNA)-PKM2 was transfected into ESCC cells. Cell migration and invasion were evaluated by wound healing and Transwell assays. Apoptosis and cell cycle were analyzed by flow cytometry (FCM). PKM2 expression was significantly higher in ESCC tissues (77.2 %, 78/101) compared with matched NAT (P = 0.003) and also higher in serum samples of Kazakh's ESCC patients (78.84 ng/mL) compared with healthy subjects (13.55 ng/mL) (P = 0.001). Patients with overexpression of PKM2 had a poor prognosis (P = 0.032). After knockdown of PKM2, cell proliferation, migration, and invasion were significantly reduced (P = 0.001), apoptosis increased (P = 0.001), and cell cycle was arrested at G1 phase. PKM2 overexpression was significantly correlated with the worse outcome of Kazakh's ESCC. Furthermore, PKM2 was involved in progression of ESCC by promoting proliferation and suppressing apoptosis, accelerating invasion, and influencing cell cycle. PKM2 could be a potential biomarker for molecular classification of ESCC.