Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidences regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels are scarce. In the present study, our aim was to investigate the impact of individual and mixed OPEs exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp) as well as 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increase risk of HPL in age ≤45 group. Bis (2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24 kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized Weighted Quantile Sum Regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in total population, as well as a positive effect of them on HPL in the subgroup of age ≤45 year, which is consistent with the individual analyses. Furthermore, joint effect analyses of revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyle had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.