Objective：To study the effect of S-adenosylmethionine（SAM） on the proliferation and migration of bladder cancer（BCa） cells via hepatocyte cell adhesion molecule（hepaCAM） and its potential molecular mechanism. Methods：T24 and BIU cells cultured in vitro were treated with different concentrations of SAM，and the effect of SAM on cell proliferation was evaluated by MTT assay. After treatment of T24 and BIU cells with different concentrations（0，0.8，1.6 mmol/L） of SAM for 72 h，real-time PCR and Western blot were used to measure the expression of methyl-CpG-binding domain protein 2（MBD2），histone deacetylase 1（HDAC1），and hepaCAM；wound healing assay and Transwell assay were used to measure the migration of cells in each group；colony formation assay was used to measure the colony formation ability of cells in each group. Results：SAM showed an inhibitory effect on the growth of T24 and BIU cells in a manner positively correlated with the con－centration and duration of treatment. After treatment of T24 and BIU cells with 0.8 mmol/L SAM for 72 h，the mRNA and pro－tein expression levels of MBD2 decreased significantly com－pared with those in the 0 mmol/L group（mRNA：P=0.048 and 0.038，respectively；protein：P=0.001 and 0.000，respectively）；the mRNA expression level of HepaCAM increased significantly（P=0.003 and 0.008，respectively），but there were no significant differences in the protein expression level of HepaCAM（P=0.770 and 0.381，respectively）. After treatment of T24 cells with 0.8 mmol/L SAM for 72 h，the mRNA and protein expression levels of HDAC1 decreased significantly（P=0.000 and 0.001，respectively）；after treatment of BIU cells with 0.8 mmol/L SAM for 72 h，the protein expression level of HDAC1 decreased significantly（P=0.004），but there was no sig－nificant difference in the mRNA expression level of HDAC1（P=0.14）. After the treatment of T24 and BIU cells with 1.6 mmol/L SAM for 72 h，there were significant decreases in the mRNA and protein expression levels of MBD2（mRNA：P=0.003 and 0.000，re－spectively；protein：P=0.001 and 0.000，respectively） and HDAC1（mRNA：P=0.000 and 0.000，respectively；protein：P=0.001 and 0.000，respectively），but there were significant increases in the mRNA and protein expression levels of hepaCAM（all P=0.000）. After treat－ment of T24 and BIU cells with SAM for 72 h，cell migration was significantly inhibited as demonstrated by the wound healing assay and Transwell assay（P<0.05），and cell colony formation ability was significantly reduced as demonstrated by the colony formation assay（P<0.05）. Conclusion：SAM can inhibit the proliferation and migration of BCa cells by reversing the expression of hepaCAM via MBD2/HDAC1.