Aim To analyze the DNA demethylation effect of 5-aza-2′-deoxycytidine （5-Aza-CdR） on the expression of apolipoprotein A （ApoA） and its mechanisms in HepG2 cells. Methods HepG2 cells, high ApoA expression cell lines, were selected for our study. ①In order to get an appropriate drug concentration and effect time, HepG2 cells were treated with different concentration（0, 10, 20, 40, 80 μmol/L） and different time （12, 24, 48, 72, 96 h）, then the relative survival ratio of HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT） method. ②mRNA and protein level of ApoA and farnesoid X receptor （FXR） were measured by reverse transcription polymerase chain reaction （RT-PCR） and Western blot respectively in HepG2 cells which was treated with 5-Aza-CdR. ③DNA methylation status of FXR gene promoter in different 5-Aza-CdR concentration was analyzed by bisulfite sequencing PCR （BSP）. Results ①Results of MTT: compared with control group, at different time point （12, 24, 48, 72 h）, the survival ratio of HepG2 cells had no significant difference in 10, 20, 40 μmol/L groups （P>0.05）. But in group of 20 μmol/L 96 h, 40 μmol/L 96 h, 80 μmol/L 24 h, 80 μmol/L 48 h, 80 μmol/L 72 h and 80 μmol/L 96 h, the survival ratio of HepG2 cells had obviously significant difference. We chose 0-40 μmol/L as safe concentration range, and selected 0-72 h as appropriate time. ②Results of RT-PCR: compared with control group, the expression of ApoA mRNA were down-regulated by 5-Aza-CdR dose dependently, while the expression of FXR mRNA were up-regulated by 5-Aza-CdR dose dependently, and obvious change appeared at 40 μmol/L 72 h （P<0.05）. ③Results of Western blot: compared with control group, the expression of ApoA were down-regulated by 5-Aza-CdR dose dependently, while the expression of FXR were up-regulated by 5-Aza-CdR dose dependently, and obvious change appeared at 40 μmol/L 72 h （P<0.05）. ④Results of BSP: with the increase of concentration of 5-Aza-CdR, the methylation status of FXR gene promoter was gradually reduced, and the methylation ratio of control group was 58.3%, the 40 μmol/L group was 8.3%. Conclusion 5-Aza-CdR can promote the expression of FXR through the demethylation effect, then down-regulate the expression of ApoA.