This paper evaluates the impact of the second municipal solid waste (MSW) source separation program on municipal solid waste generation (MSWG) in China. Without considering the spatial interactions between cities, the second MSW source separation program has a nonsignificant adverse effect on the per capita municipal solid waste generation (PMSWG). Relaxing the stable-unit-treatment-value assumption (SUTVA), which holds in most of the previous estimation literature on treatment effects, involving the spatial spillover effect among cities, as well as correcting the endogenous local policy has a significantly negative but not robust impact on the PMSWG. The estimation results of the generalized nesting spatial regression models (GNS) imply that the spatial interaction characteristics among Chinese prefecture-level cities may, if neglected, lead to underestimation of the reduction effects of the second MSW source separation policy on the absolute amount of PMSWG. More importantly, our study indicates that although not all the spatial econometric models support the significant reduction effect of source separation on the absolute amount of PMSWG, the source separation program significantly reduces the relative amount of PMSWG, and this result is robust in all spatial models.