Abnormal syncytialization of cytotrophoblast (CTB) cells is known to be associated with preeclampsia (PE), yet its underlying molecular mechanisms remain elusive. In this study, proteomic analysis of placental tissues was performed to identify PE-related pathogenic genes. The results showed that NCK Adaptor Protein 1 (NCK1) was downregulated in placental tissues from patients with early-onset PE. Our work suggested that NCK1 is a potential therapeutic target for PE.