The interaction of anticancer drug etoposide (ETO) with salmon sperm double strand deoxyribonucleic acid (ss dsDNA) in aqueous solution and immobilized on a screen-printed carbon electrode (SPCE) has been thoroughly explored using voltammetric techniques. UV-vis absorption spectroscopic technique was also employed to probe the interaction between the ETO and ss dsDNA in solution. ETO showed two oxidation peaks in phosphate buffer solutions (20 mM, pH 4.5 and 7.4). The changes in the anodic current signals of ETO were monitored in the presence and absence of ss dsDNA by using an oxidized bare SPCE in connection with differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The diffusion coefficient for the free ETO was 4.2 x 10(-6) cm(2) s(-1) and 3.8 x 10(-7) cm(2) s(-1) for the ETO-DNA complex. The electrochemical indicated a 1:1 complex formation of ETO with DNA. The values of binding constant have been determined to be 4.1 x 10(5) M-1 and 4.8 x 10(5) M; and 5.2 x 105 M-1 and 5.6 x 10(5) M-1 for ETO and ETO cation free radical in phosphate buffer solutions of pH 4.5 and 7.4; respectively. The overall results suggest that ETO binds to DNA through combined effect of intercalation and electrostatic interaction. A detection scheme based on a preconcentration and DPV determination at ss dsDNA modified SPCEs (DNA/SPCEs) was proposed for the trace determination of the ETO. The developed method was successfully applied to the determination of the ETO in spiked human serum samples. (C) 2013 Elsevier Ltd. All rights reserved.