Recently, the Ras association domain family 1 (RASSF1) gene has been identified as a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor. However, the function of RASSF1C, both in normal and cancer cells, is still unknown. In order to learn more about the function of RASSF1C in human cancer cells, we tested the effect of silencing RASSF1C mRNA using small interfering RNA on lung cancer cells (NCI H1299) that express RASSF1C but not RASSF1A. Small interfering RNA specific for RASSF1C reduced RASSF1C mRNA levels compared to controls. This reduction of RASSF1C expression caused a significant decrease in lung cancer cell proliferation. Furthermore, over-expression of RASSF1C increased cell proliferation in lung cancer cells. Lastly, we found that RASSF1C, unlike RASSF1A, does not up-regulate N-cadherin 2 and transglutaminase 2 protein expression in NCI H1299 lung cancer cells. This suggests that RASSF1C and RASSF1A have different effector targets. Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but rather stimulates lung cancer cell proliferation.