The widespread use of nanoparticles (NPs) and organic pollutants increases the risk of their coexistence in the aquatic environments. It is uncertain how the combined toxicities of NPs and OCs affect aquatic organisms in surface waters. In this study, the binary combined toxicities of TiO2 NPs with three different organochlorines (OCs)-pentachlorobenzene (PeCB), 3,3,4,4-tetrachlorobiphenyl (PCB-77), and atrazine on Chlorella pyrenoidosa in three karst surface water bodies were investigated. The correlation analysis results indicated that the toxicities of TiO2 NPs and OCs to algae were mainly related to the total organic carbon (TOC) and ionic strength of surface water. Surface water relieved the growth inhibition of the pollutants on algae as compared with ultrapure water (UW). The combined toxic effect caused by the co-exposure of TiO2 NPs-atrazine was synergistic and had an antagonistic effect for TiO2 NPs-PCB-77 in four types of water bodies. However, the co-exposure of TiO2 NPs-PeCB had an additive effect in the Huaxi Reservoir (HX) and synergistic effects in Baihua Lake (BH), Hongfeng Lake (HF), and UW. TiO2 NPs increased the bioaccumulation of OCs by algae. Both PeCB and atrazine significantly increased the bioaccumulation of TiO2 NPs by algae, except for PeCB in HX; however, PCB-77 reduced the bioaccumulation of TiO2 NPs by algae. The toxic effects of TiO2 NPs and OCs on algae in different water bodies were the result of the nature of the pollutants, bioaccumulation, hydrochemical properties, and other factors.