Cardiac Na+/Ca2+ exchanger 1 (NCX1) expression levels change under various pathophysiological conditions. However, its mechanism is unknown. We found that fluvastatin, an HMG-CoA reductase inhibitor, decreased NCX1 mRNA and protein by inhibiting a small G protein, RhoB, in H9c2 cardiomyoblasts. Conversely, lysophosphatidylcholine (LPC) increased NCX1 mRNA and protein by activating RhoB. The effect of LPC was mediated by geranylgeranylation but not farnesylation of RhoB. Furthermore, we also detected that activation of RhoB increased NCX1 mRNA stability. Our results suggest that RhoB is involved in modulation of cardiac NCX1 mRNA expression.