Placenta growth factor (PlGF) is a member of the VEGF family and has been implicated in the aggressive capacity of solid tumours, partly via its impact on angiogenesis. The present study determined the direct biological function of endogenous PlGF in lung cancer cells. From the human non-small cell lung cancer cell line A549 which expressed good level of PlGF, we created sublines within which PlGF expression was knockdown by way of anti-PlGF ribozyme transgenes. Remarkable reductions of both PlGF mRNA and protein by the ribozyme transgenes were revealed in A549 transfectants (A549(DeltaPlGF)) using RT-PCR and Western blotting respectively. A549(DeltaPlGF) cells exhibited significantly reduced migration and adhesion compared with the wild-type (A549(WT)) and the empty plasmid control (A549(pEF/His)) cells. Immunocytochemistry and Western blotting further revealed that the expression of ROCK1, Rho associated kinase, was also reduced in A549(DeltaPlGF) cells, in comparison with wild-type and control cells. In addition, A549(DeltaPlGF) cells lost its response to a ROCK inhibitor, which otherwise strongly inhibited the motility of A549(WT) and A549(pEF/His) cells. These data indicate that PlGF directly regulates the motility of human lung cancer cells and that this regulation critically dependent on ROCK-1. The study further indicates that PlGF is a potential therapeutic target in lung cancer.