Water quality criteria for the protection of human health (HHWQC) are crucial for the management of aquatic environmental quality. However, previous studies derived HHWQC using only deterministic approaches, which may under/overprotect target populations. This paper improved the methodology for criteria development and applied it to organophosphate esters (OPEs). Missing model parameters, including the trophic level-specific fish consumption rate (FI n ) and lipid fraction (f l(TL,n) ), were derived according to China's conditions. The trophic level-specific national bioaccumulation factors (BAFs) for OPEs (5.05−14,281 L/kg) were calculated based on fieldmeasured BAFs in surface freshwater across China and were dominated by the hydrophobicity of compounds. Then, the probabilistic approach was introduced to HHWQC derivation (0.1120−400.5 μg/L), and the results were compared with those derived by the deterministic method (0.1024−664.5 μg/L), which demonstrated that the probabilistic approach derived HHWQC more accurately. The contributions of organism ingestion to the HHWQC for OPEs were steady (<10%) with log K ow <3.5, increased linearly (10−90%) within a log K ow of 3.5−5.5, and then leveled off. Regarding the effects of carcinogenic OPEs, approximately 10% of the studied freshwater in China displays significant risks to human health. This study is significant for the scientific development of HHWQC worldwide and the management of pollutants in water.