Abstract Wastewater-based epidemiology combining with a population model based on hydrochemical parameters was applied in 10 wastewater treatment plants (WWTPs) in Jilin province, China. Population of WWTPs served was calculated by the model including three hydrochemical parameters ammonia nitrogen, chemical oxygen demand, and total phosphorus. The population model was constructed by using analytic hierarchy process to calculate weight factors of each hydrochemical parameters equivalent population. The size of population estimated by the model showed the highest correlations with cotinine mass load (r 2 = 0.91, p < 0.001), demonstrating better population estimation. Meanwhile daily excretion of cotinine per capita was first estimated about 0.68 mg in China through liner regression analysis. In accessing the viability of the population model, the abuse of methamphetamine (METH) was calculated. Prevalence of METH use in Jilin province was calculated with an average of 0.72% based on the population model, which was similar with the result reported by United Nations World Drug Report in 2018. In assessing uncertainty of different population estimations, population model showed lower uncertainty than single hydrochemical equivalent population. These results indicate the population model based on hydrochemical parameters reduces uncertainty in population estimation and is a useful tool in monitoring illicit drug abuse. Graphical abstract Unlabelled Image Highlights • Population model was built through hydrochemical parameters. • Analytic hierarchy process was used to calculate weight factors for each parameter. • Population model based on multi-parameters showed low uncertainty. • Methamphetamine prevalence in Jilin province was estimated to be 0.6%. [ABSTRACT FROM AUTHOR]