Ether lipids have been implicated in the exacerbation of human tumors. Accumulating evidence suggests that the alkylglycerone phosphate synthase (AGPS) is involved in the suppression of some types of tumor. However, the role and molecular mechanism of AGPS in the invasion of human glioma and hepatic carcinoma remain unclear. In the present study, using AGPS-knockdown human glioma U87 and hepatic carcinoma HepG2 cell lines, we explored the role of AGPS, as well as its molecular mechanism, in invasion in vitro. It was demonstrated that silencing AGPS expression resulted in a decreased expression of cellular lipids such as LPA, LPAe and PGE2, adhesion, invasion potential and arrested cell cycle in tumor cells. The expression of invasion-related genes such as MMP-2/9, E-cadherin and CD44 showed marked changes in AGPS‑knockdown cells. In addition, we found that AGPS regulated the activity of the MAPK pathway, as well as the transcriptional activity of Twist, AP-1, and Snail. The results demonstrated that AGPS negatively regulated the invasion potential of glioma and hepatic carcinoma cells by modulating the expression of relevant genes and activity of the MAPK pathway. Therefore, AGPS may be a potential glioma and hepatic carcinoma therapeutic target.