Objective To investigate the effect of acetyl coenzyme A synthase 2 (ACSS2) on the migration and invasion induced by nutrient stress (NS) in cervical cancer cells. Methods Immunohistochemistry was used to detect the expression and distribution of ACSS2 protein in 20 pairs of cervical tumors and their adjacent normal tissues. Cervical cancer HeLa cells and the normal cervical epithelial HCvEpC cells were cultured, and serum content in culture medium was reduced from 100 to 10 mL/L as NS treatment. Western blot analysis was performed to detect the expression of ACSS2, GSK-3β, p-GSK-3β, β-catenin, β-actin, E-cadherin, vimentin. Small interfering RNA (siRNA) was used to down-regulate the expression of ACSS2. Cell migration was assessed by wound healing test, and cell invasion was tested by TranswellTM assay. Results The expression level of ACSS2 in 20 cervical tumors was significantly higher as compared with the adjacent normal tissues. The levels of ACSS2 in HeLa cells could be significantly up-regulated by NS, while no marked change was seen in HCvEpC cells. The treatment of NS promoted the epithelial mesenchymal transformation (EMT) of HeLa cells, which could be effectively reversed by siRNA-ACSS2. The scratch results showed that NS increased the healing rate of HeLa cells, which could be blocked by ACSS2 silencing. Coincidently, the number of invasive cells was elevated after NS treatment, which could be partly reversed by siRNA-ACSS2. The expression of ACSS2, p-GSK-3β and nuclear β-catenin was up-regulated in HeLa cells treated with NS for 48 hours, while siRNA-ACSS2 down-regulated their expression. Conclusion Silencing ACSS2 expression inhibits migration and invasion of cervical cancer cells induced by NS, which is related to down-regulated Wnt/β-catenin signaling pathway activity.