In our work, operation of hybrid desiccant cooling system (HDCS) has been investigated based on experimental studies. Different climates have been created by changing the temperature and humidity of HDCS inlet air, using an electrical heater and a centrifuge humidifier. Input energies, temperature of various points, and their relative humidity have been measured at the created climates. Coefficient of performance (COP), thermal coefficient of performance, and electrical coefficient of performance (ECOP) of the HDCS have been calculated. As a reference situation, vapor compression system (VCS) was examined at the same condition as HDCS. Results show that COP of HDCS in comparison with VCS decreased about 36% and 28% in hot-dry and hot-humid climates, respectively, which is due to the thermal energy consumption in HDCS. In contrast its ECOP increased, which means that by using HDCS some electrical energy would be saved. Defining operating cost index (OCI) parameter, operation costs of VCS and HDCS have been compared. Analyzing the OCI results shows that in HDCS, although decreasing the electricity consumption results in more usage of natural gas, these systems are economical especially in those countries with low natural gas prices.