The phosphodiesterase 4B (PDE4B) is a candidate susceptibility gene for schizophrenia (SCZ), interacting with DISC1, a known genetic risk factor for SCZ. To examine if variants within PDE4B gene are associated with SCZ in Northwestern Han Chinese, and if these effects vary in gender-specific subgroup, we analyzed 20 SNPs, selected from previous studies and preliminary HapMap data analyses with minor allele frequency (MAF) ≥ 20%, in a cohort of 428 cases and 572 controls from genetically independent Northwestern Han Chinese. Single SNP association, haplotype association and sex-specific association analysis were performed. We found that rs472952 is significantly associated with SCZ and rs7537440 is associated with SCZ in females. Further analysis indicated that a haplotype block spanning PDE4B2 splice site is highly associated with SCZ and several haplotypes in this block have about twofold to threefold increase in cases. Our results provide further evidence that PDE4B may play important roles in the etiology of SCZ.