Aim To reduce the level of apolipoprotein B (Apo B) via the inhibitory effect of antisense oligodeoxynucleotides (AODN) on expression of Apo B gene in cultured liver cells and search its mechanism. Methods The cultured liver cells were treated with synthesized Apo B gene antisense, sense ODN (SODN) and 0.9% salt solution respectively. Apo B100 concentration was measured by Auto-biochemical Instruction. The mRNA level was observed by using of reverse transciption-polymerase chain reaction (RT-PCR). Results Apo B gene AODN 5, 10, 15, and 20 μmol/L inhibited Apo B concentration 26.6%, 34.2%, 34.2%, and 45.8% respectively. The inhibitory effect appeared in a concentration-dependent manner. RT-PCR showed that Apo B gene AODN downregulated Apo B mRNA expression obviously. Conclusions he ApoB gene AODN inhibited Apo B gene expression obviously and reduced Apo B concentration. The possible mechanisms are to downregulate Apo B mRNA level and inhibit translation of Apo B gene.