OBJECTIVE To investigate the antitumor effect of the low-voltage electric pulses (LVEPs) on melanoma-bearing mice. METHODS Tumor models were established by subcutaneously inoculating BALB/c mice with B16F10 melanoma cells. These mice were randomly divided into control group and treated groups which were exposed to electric pulses of different frequency 10, 20, 30 Hz for consecutive 20 days with 30 minutes per day. In every day, tumor size was measured, and morphological changes of tumors were observed by HE staining. The expressions of caspase-3 and matrix metalloproteinase-9 (MMP-9) mRNAs were tested by real-time quantitative PCR, and the expressions of caspase-3 and MMP-9 proteins were detected by immunohistochemistry. RESULTS Compared with the control group, seven days after LVEPs treatment, the tumor size in 30Hz treated group was reduced significantly; twenty days after treatment, the tumor size of all treated groups diminished significantly. The tumor growth inhibition rate increased with time. Compared with the control group, nuclear shrinkage and necrosis of more tumor cells were found in the treated groups; the expression of caspase-3 mRNA and protein was significantly enhanced in the treated groups; the expression of MMP-9 mRNA and protein was significantly depressed in the treated groups; and the changes of caspase-3 and MMP-9 expressions became greater with the frequency increasing. CONCLUSIONS LVEPs can induce the activation of caspase-3, suppress the expression of MMP-9, and inhibit tumor growth.