Lung cancer is the leading cause of cancer-related death worldwide. Transforming growth factor-β receptor II (TGF-βRII) plays an important role in the regulation of proliferation and progression in cancer. Statins have been documented to exhibit anticancer and cancer chemopreventive properties. However, the effects and mechanisms of simvastatin on the development of lung cancer are still unclear. In the present study, quiescent A549 cells were treated in vitro with fetal bovine serum (FBS) in the presence or absence of simvastatin. MTT, Western blot, and real-time qPCR were used to detect cell viability, activation of ERK, and expression of TGF-βRII at the protein and RNA level. Our results demonstrated that simvastatin inhibited activation of ERK, downregulated expression of TGF-βRII, and suppressed A549 cell proliferation. Furthermore, the effects of simvastatin can be reversed by farnesyl pyrophosphate (FPP). Therefore, these results suggest that simvastatin may inhibit A549 cell proliferation and downregulate TGF-βRII expression by inhibiting activation of ERK. Our findings may advance the current understanding of the effects of simvastatin on cancer progression and contribute to the study of cancer treatment.