By using a liquid desiccant ventilation system for dehumidification and an air-handling unit for cooling, the liquid desiccant cooling system (LDCS) system became a promising alternative for traditional technology. Solar thermal energy is suitable to deal with the heat requirement of LDCS in buildings, especially in the areas with abundant solar radiation. The energy saving of solar-assisted liquid desiccant air-conditioning system is significantly affected by various operation conditions, and multi-parameter optimization was necessary to improve the system applicability. In this paper, we investigated the impact of five main parameters on the system performance via self-developed system modelling, including the solution mass flow rate, concentration, cooling tower flow rate, and solar water flow rate and installation area of solar collector. A typical commercial building in Hong Kong was selected as a case study, which air-conditioning load was obtained by Energy-plus. The results indicated that the installation area of solar collector showed the greatest impact, and the effect of heating water flow rate was also important. The effect of desiccant flow rate was significant, but the influence of solution concentration was slight. Then, the multi-parameter optimization was conducted for obtaining a maximum annual electricity saving rate based on the Multi-Population Genetic Algorithm. The optimized installation area of solar collector was 72 m2, and the heating water flow rate was 0.66 kg/s. The optimized solution flow rate was 0.17 kg/s. The required cooling water flow rate was around 0.8 kg/s.