Dietary polyphenols have been reported as an effective phytochemical for health protection and cinnamic acid (CA) is one of the polyphenols that has been demonstrated having chemopreventive potential. It was known that the early and distal metastasis might lead to the high mortality of patients with lung adenocarcinoma. We previously compared and verified the inhibitory effect of cis-CA and trans-CA on phorbol-12-myristate-13-acetate (PMA)-induced invasion of human lung adenocarcinoma A549 cells. The aim of this study was to explore the underlying molecular mechanism. By gelatin zymography and semi-quantitative RT-PCR, the activities and mRNA of MMP-9/MMP-2 exerted a significantly (p<.05) dose-dependent reduction by treating with cis-CA and trans-CA. Western blots further showed that the cis-CA- and trans-CA-inhibited MMPs might partly through modulating TIMP-1 and the PAI-2-regulated uPA activity. In molecular level, the AP-1 and NF-κB as well as the downstream of the MAPK pathway might be involved in cis-CA- and trans-CA-inhibited MMPs expression. This study disclosed the molecular mechanism underlying the anti-invasive activity of cis-CA and trans-CA and concluded the cis- and trans-form of CA should be a safe and potential agent to prevent lung tumor cells from metastasizing.