Cold atmospheric plasma, a promising technology for cancer therapy, can simultaneously induce electrochemistry, which has been widely demonstrated to be effective against cancer. Herein, the anticancer effects of direct current plasma jets and electrochemical circuit are comparatively studied with similar topological structures and average currents. The cell inactivation patterns formed by plasma and electrochemical treatment (EChT) are disparate, and the inactivation is mainly caused by the emission of charged species, helium flow, in situ OH radical production, or local alkalization. The culture medium treated by EChT exerted no sustained anticancer effect, whereas the medium treated by plasma could maintain a strong effect due to the production of more reactive species, suggesting that the electrochemistry does not dominate the plasma inactivation of cancer cells.