This study was designed to investigate the molecular mechanism of mercury (Hg) toxicity in the newborns by mRNA sequencing (mRNA-seq). A questionnaire survey, routine blood parameters of pregnant women, and umbilical cord blood (UCB) of newborns were collected. The median (25th percentile, 75th percentile) of total Hg (THg) concentrations in UCB of newborns was 3.63 (2.50, 6.19) mu g/L. A total of 504 differentially expressed genes of mRNA were revealed between the case and control group, including 456 upregulated and 48 downregulated genes. The Gene Ontology (GO) analysis showed that differentially expressed genes were primarily involved in mitophagy, hemoglobin complex, and oxygen carrier activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the most differentially expressed genes were annotated in Huntington's disease, Parkinson's disease, and Alzheimer's disease. The qRT-PCR was used to validate the results of mRNA-seq. Low-dose Hg exposure could increase blood NE# and WBC in the pregnant women. This study provides scientific evidences on mechanism of Hg toxicity in newborns.