Protocadherin18b (Pcdh18b) belongs to the protocadherins, which make up the largest subgroup within the cadherin superfamily. To study the role of pcdh18b on embryonic neurogenesis in zebrafish, one type of well designed antisense morpholino oligonucleotide was injected into one or two-cell stage embryos to block the translation of pcdh18b. After injection, the phenotypes of nervous system were monitored by whole mount in situ hybridization and acridine orange staining. Whole-mount in situ hybridization with neurog1, elavl3, gfap and krox20 RNA probes showed that the expression of neural precursor cells, neurons, neuroglia cells and rhombencephalon3, 5 was strikingly affected; meanwhile, the expression of MHB (midbrain-hindbrain boundary) markers pax2a and wnt1 was significantly compromised and showed duplication of neural tube in pcdh18b down regulation group. Acridine orange staining pointed out that down regulation of pcdh18b increased cell apoptosis in midbrain, hindbrain and MHB region. These results suggest that pcdh18b plays an important role in the zebrafish neurogenesis.