This study was to explore the relationships between NOTCH4 gene and schizophrenia (SP) and mood disorders (MD), and to search for a common susceptible gene for SP and MD in Chinese Han population. We collected 61 mixed pedigrees of SP and MD in Chinese Han population. NOTCH4 polymorphisms -1725T/G and-25T/C were genotyped by applying PCR-RLFP technique, then transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk analysis(HHRR) were performed. The results showed that -1725T/G was not associated with SP or MD (P>0.05), -25T/C was not associated with SP (P>0.05), but associated significantly with MD for female or early-onset (age of onset<or=25 years) group (P<0.05), and - 1725G/-25T haplotype was significantly associated with SP (P<0.05), but not associated with MD (P>0.05). Our results suggested NOTCH4 or neighboring gene might be a common susceptible gene for SP and MD in the pedigrees studied.