To investigate the interaction between the single nucleotide polymorphism of the 3' untranslated region (3'UTR) of the pentraxin 3 (PTX3) gene, as well as environmental factors and the preeclampsia risk in a Chinese Han population.Sanger sequencing was used to analyze rs5853783 and rs73158510 loci of the PTX3 gene 3'UTR from 235 patients with preeclampsia and 235 control subjects. The plasma PTX3 protein level was measured by enzyme-linked immunosorbent assay (ELISA).The risk of preeclampsia in the PTX3 gene rs5853783 locus D allele carriers was 0.72 times higher than that of the I allele carriers (95% CI: 0.60-0.84, P < .001). The risk of preeclampsia in the PTX3 gene rs73158510 locus A allele carriers was 1.36 times higher than in the G allele carriers (95% CI: 1.16-1.55, P < .001). The area under the ROC curve (AUC) for the diagnosis of preeclampsia by plasma PTX3 protein levels was 0.906 (P < .001). The PTX3 gene rs5853783 and rs73158510 single nucleotide polymorphisms (SNPs) were associated with plasma PTX3 protein levels. The AUC of plasma PTX3 protein level diagnosis of preeclampsia in PTX3 gene rs5853783 locus II genotype subjects was up to 0.9371, followed by the ID genotype (AUC = 0.8586); the DD genotype was the lowest (AUC = 0.8154). The AUC of plasma PTX3 protein level diagnosis of preeclampsia in rs73158510 locus GG genotype subjects was 0.9102, GA genotype was 0.8766, and AA genotype was 0.8750.The rs5853783 and rs73158510 SNPs in the 3'UTR region of the PTX3 gene are associated with the risk of preeclampsia in a Chinese Han population.