Abstract: Objective To investigate the expression and its possible function of AMP-activated protein kinase(AMPK) in the occurrence of esophageal squamous cell carcinoma(ESCC). Methods The tissue samples were collected from 40 fresh ESCC and 40 normal esophagus, and the expression of AMPK downstream substrates p-ACC and ACC were tested by Western-blot, then the correlations of p-ACC and ACC expression to the clinicopathologic characterisics were analyzed. Results The expression of p-ACC in ESCC was lower than that in normal tissues, with significant statistical difference (P<0.05). The down-regulation ratio of p-ACC in poorly-differentiated ESCC was 81.8%(9/11), which was significantly higher than that in moderately and well-differentiated ESCC(3.5%, 1/29). There was no correlation of p-ACC down-regulation with age, gender, TNM stage and lymph node metastasis(P>0.05). Conclusion The expression of p-ACC was down-regulation in ESCC, and the down-regulation is associated with tumor cell differentiation.