Discovering new anticancer agents and analyzing their activities is a vital part of drug development, but it requires a huge amount of time and resources, leading to the increasing demands for more-effective techniques. Herein, a novel and simple cell-based electrochemical biosensor, referred to as a cytosensor, was proposed to investigate the electrochemical behavior of human skin malignant melanoma (SK-MEL28) cells and the anticancer effect of saponin on cell viability. To enhance both electrocatalytic properties and biocompatibility, gold nanoparticles were electrochemically deposited onto a conductive substrate, and poly-L-lysine was further added to the electrode surface. Electric signals from SK-MEL28 cells on the electrodes were obtained from cyclic voltammetry and differential pulse voltammetry. The cathodic peak current was proportional to the cell viability and showed a detection range of 2,880-40,000 cells per device with an excellent linear cell number-intensity relationship (R= 0.9952). Furthermore, the anticancer effect of saponin on SK-MEL28 cells was clearly established at concentrations higher than 20 μM, which was highly consistent with conventional assays. Moreover, the developed electrochemical cytosensor for evaluating anticancer effects enabled rapid (<2 min), sensitive (LOQ: 2,880cells/device), and non-invasive measurements, thus providing a new avenue for assessing the anticancer drugs in vitro.Copyright © 2021 Elsevier B.V. All rights reserved.