Previous studies have suggested an adverse association between exposure to organophosphate esters (OPEs) and metabolic disorders. However, there is still limited evidence regarding the link between OPEs and metabolic dysfunction-associated fatty liver disease (MAFLD). Moreover, it remains uncertain whether the impact of OPEs on MAFLD is consistent across genders. This study aimed to investigate the associations of OPEs with MAFLD and to explore potential gender differences in these associations. We recruited 1863 participants from Wuhan, China, and measured the levels of fifteen urinary OPE metabolites. Logistic regression and weighted quantile sum (WQS) regression were utilized for single-pollutant and multi-pollutant analysis, respectively. Moreover, stratified and interaction analyses were performed to assess potential sex-specific associations. The results of single-pollutant analysis showed that participants in the highest tertile of BCIPHIPP (OR = 1.48, 95% CI = 1.11, 1.99) and BDCIPP (OR = 1.51; 95% CI = 1.12, 2.03) had a higher odds ratio of MAFLD compared to those in the lowest tertile. WQS regression revealed a detrimental effect of OPEs mixture on MAFLD (OR = 1.40, 95% CI = 1.19, 1.61), with BCIPHIPP (49.3%), and BDCIPP (29.5%) being the major contributors. Sex-specific analyses demonstrated that the positive association of OPEs with MAFLD was only observed in male participants. In conclusion, exposure to the mixture of OPEs was positively correlated with MAFLD and this adverse effect was more evident among men.