With the rapid development of economy and the fast growing of the world’s population,demands for energy are increasing markedly. On the other hand, industrial contaminants anddomestic wastewater are also constantly increasing. The simultaneous production of energy and wastewater treatment can provide economic and environmental benefits by using microbial fuelcells (MFCs) [1]. Wastewaters are renewable energy resources in the form of biodegradableorganic matters. It means that renewable energy, which reduces greenhouse gas emissions can be extracted from wastewater [2]. MFCs are bio-electrochemical systems that convert the chemical energy of organic waste material to electrical energy by using bacteria as biocatalysts [3]. Atypical MFC is composed of two compartments, anodic and cathodic chambers separated by proton/cation exchange membrane. Generally, the bacteria at the anode chamber decompose organic material to proton and electron anaerobically. The electrons are transferred from theanode electrode to the cathode electrode through an external circuit. The protons migrate to cathode through proton exchange membrane separator. Electrons in the cathodic chamber combine with protons and oxygen to produce water (Fig. 1) [4]. Many factors influence on theelectrochemical performance of a MFC system. Among all factors, the cathode as a significant performance-limiting component and the reduction kinetics in MFCs has a great effect on the electricity generation characteristics [5]. At the present study, low-cost and high performance MFC was developed by using DNA as a final electron acceptor in the cathodic chamber. Singlestranded DNA was employed for the modification of carbon paste electrode (ssDNA/CPE) as bio-cathode in the MFC to enhance its performance. When the bare CPE was used as cathode the MFC got the power density of 3.01 mW m-2 at a current density of 28.70 mA m-2, whereas if the ssDNA/CPE was used as bio-cathode, the maximum power density was increased to 501.87mW m-2 at a current density of 1190.77 mA m-2, indicating ssDNA/CPE provided high catalytic activity for reduction reaction in cathodic chamber. While the internal resistance in water without aeration was accounted 352.04 Ω and 42.51 Ω for the bare CPE and ssDNA/CPE as cathodeelectrodes, respectively. Therefore, use of ssDNA/CPE as a bio-cathode markedly improved the performance of a MFC system compared with a MFC using CPE. Finally, the effect of DNA sequence composed of pure bases involved only adenine, cytosine, thymine and guanine sequences was examined in MFC output.