Organophosphate flame retardants (OPFRs), used as flame retardants and plasticizers, have been suggested to impair fetal growth and development in toxicological studies, but epidemiological data are extremely limited. This study was designed to explore whether prenatal exposure to OPFRs was associated with an increased risk of low birth weight (LBW) using a nested case-control design based on the ongoing prospective birth cohort in Wuhan, China. A total of 113 cases and 226 matched controls recruited from this cohort project in 2014-2016 were included. OPFR metabolite concentrations in maternal urine samples collected in the third trimester were determined, and birth outcomes were extracted from medical records. Compared with the lowest tertile of diphenyl phosphate (DPHP) concentrations, pregnant women with the highest tertile of DPHP had a 4.62-fold (95% confidence interval (CI): 1.72, 12.40) significantly increased risk for giving birth to LBW infants, with a significant dose-response relationship (p-trend < 0.01). After stratification by newborn sex, the significant positive association of DPHP levels with LBW risk was merely observed among female newborns. Our results suggest a positive association between maternal urinary DPHP concentrations and LBW risk for the first time, and the effect appears be sex-specific.