To explore the effect of formaldehyde on DNA-protein cross-links (DPC) in eucaryotic cells and prokaryotic cells, Pichia pastoris and E.coli DH5α were chosen as materials to evaluate the amount of DPC induced by liquid formaldehyde in vivo by the method of KCl-SDS assay. The results showed that formaldehyde could not induce DPC at low dose(25μmol/L,P>0.05), but could obviously induce DPC at higher dose (125 and 625μmol/L,P<0.05). The DPC coefficient in Pichia pastoris was 10-fold higher than that in E.coli DH5α. It is concluded that formaldehyde could induce DPC in eucaryotic cells and prokaryotic cells with a dose-dependent manner and the DPC coefficient in Pichia pastoris is higher than that in E.coli DH5α.