Recent advances in the study of microRNAs indicate that they have an important role in regulating cellular activities such as proliferation, morphogenesis, apoptosis and differentiation by regulating the expression of various genes. MiR-199a-3p is highly expressed in hair follicles and in some tumor cells, suggesting its participation in tumor progression, but it is significantly underexpressed in hepatocellular carcinoma and in bladder cancer. The mechanism underlying these effects is not yet known. Here, we dissect the effects of miR-199a-3p on YPEN-1 endothelial cells, and MDA-MB-231 and MT-1 breast cancer cell lines. We found that expression of miR-199a-3p promotes proliferation and survival of endothelial cells as well as breast cancer cells. Remarkably, miR-199a-3p inhibited both endogenous caveolin-2 activity and exogenous caveolin-2 activity, which was confirmed by a reporter construct bearing the 3'-untranslated region of caveolin-2. However, overexpression of caveolin-2 completely counteracted the enhancement of miR-199a-3p-mediated activities on cell proliferation, survival and sensitivity of tumor cells to anticancer drugs. Our findings suggest that MiR-199a-3p targeting of caveolin-2 might have an important role in breast cancer tumor progression, making it a potential candidate for intervention in cancer.