The objective of this study is to understand the effects of operating conditions and cathode parameters on the salt removal performance of hybrid capacitive deionization systems (HCDI). Hence, the effects of half cycle length, flow rate, cathode thickness, and conductive additive loading in the cathode are systematically investigated. Hydrothermally synthesized alpha-MnO2 was selected as the active material in the cathode. Desalination results indicate notable dependence of HCDI performance on the investigated parameters. For instance, increasing half cycle length increases the salt adsorption capacity (SAC) by similar to 58% but decreases the peak salt adsorption rate (PSAR) by similar to 28%. On the other hand, increasing the flow rate leads to an increase of the SAC and PSAR by similar to 25% and similar to 115%, respectively. Increase in the cathode thickness also showed a notable decay in performance with 43% drop in SAC. The amount of conductive additive in the cathode was also investigated to observe the impact of electrical conductivity on the CDI performance. Salt adsorption capacity and rate of HCDI systems containing identical active materials show strong dependence on the operation conditions and cathode parameters, which suggests a necessity of developing an understanding of the impact of these conditions on the system performance.