Pulsed electric fields with nanosecond duration and high amplitude have effects on biological subjects and bring new venue in disease diagnosis and therapy. To address this respect, we investigated the responses of paired tumor and normal human skin cells - a basal cell carcinoma (BCC) cell line, and its sister normal cell line (TE) - to nanosecond, megavolt-per-meter pulses. When BCC (TE 354.T) and TE (TE 353.SK) cells, cultured under standard conditions, were exposed to 30 ns, 3 MV/m, 50 Hz pulses and tested for membrane permeabilization, viability, morphology, and caspase activation, we found that nanoelectropulse exposure: 1) increased cell membrane permeability in both cell lines but to a greater extent in BCC cells than in normal cells; 2) decreased cell viabilities with BCC cells affected more than normal cells; 3) induced morphological changes in both cell lines including condensed and fragmented chromatin with enlarged nuclei; 4) induced about twice as much caspase activation in BCC cells compared to normal cells. We concluded that in paired tumor and normal skin cell lines, the response of the tumor cells to nanoelectropulse exposure is stronger than the response of normal cells, indicating the potential for selectivity in therapeutic applications.