Background and Objective: In recent years, management and disposal of municipal solid waste has become a global problem and the most important environmental concern. Anaerobic digestion is a cost-effective solution for treatment of both solid waste and wastewater. The aim of this study was to investigate the positive or negative effects of calcium chloride content in anaerobic digestion process of municipal solid waste and leachate on biogas production. Materials and Methods: Experiments with 8 levels of calcium chloride on co-digestion of municipal solid waste and leachate were investigated in 500 ml digesters under mesophilic conditions in a completely randomized design with three replications. Reactors with a ratio of substrate to inoculum of 2 (on VS basis) were operated and the volume of the biogas was measured daily. Volatile and total solids, carbon/nitrogen of waste, COD, BOD and heavy metals were measured by following APHA. Results: The results of the experiment showed that the pH was decreased with increasing calcium chloride concentration. The highest amount of cumulative biogas production was obtained in CaCl2 of 2 g/L with the highest VS and TS reduction. Higher concentrations of CaCl2 (≥3 g/L) caused a reduction in the degradability of volatile and total solids and, as a result, a decreased performance of the digester. Conclusion: The results clearly confirmed that the addition of calcium chloride was an effective solution to improve biodegradability in co-digestion of the MSW and leachate and consequently to reduce the total and volatile solids and to increase the amount of‌ biogas.