Abstract Despite advances in treatment, breast cancer remains one of the leading causes of death, and obviously new approaches to the treatment are needed. Due to minimal side effects, unlike more aggressive forms of therapy such as chemotherapy and radiotherapy, the application of irreversible electroporation-electrochemotherapy represents a new modality in the treatment of cancer. Electrochemotherapy uses an electric field (375 V cm ^-1) to allow increased absorption of chemotherapeutic drugs selectively in tumor cells. Accordingly, the total dose of these agents can be significantly reduced and numerous side effects can be avoided in this way. The Real Time Cell Analysis-RTCA-xCELLigence system was used to monitor the cytotoxic effects of the treatment. The results confirmed the justification of the use of paclitaxel in chemotherapy and showed cytotoxic effects of paclitaxel which were time and dose-dependent in both cell lines. When paclitaxel was administered in combination with an electric field, in both cell lines, the results showed a greater cytotoxic effect compared to the same treatment without electrochemotherapy. MCF-7 cells are more sensitive to electrochemotherapy treatment with paclitaxel compared to MDA-MB-231. Electrochemotherapy using paclitaxel in MCF-7 cells had a 6.4-fold higher cytotoxicity compared to the treatment only with paclitaxel. The results obtained support the current knowledge of the benefits of electrochemotherapy. It has been shown that electrochemotherapy can significantly increase the effects of paclitaxel in the tested cell lines. In this way, a very high concentration of chemotherapeutics in the targeted tissue was achieved, which represents localized chemotherapy.