A series of paeonol derivatives have been synthesized by simple acylation and etherification of the paeonol.  Anti-tumor activities of the synthesized compounds were evaluated against HeLa and MCF-7 cells lines in vitro by the standard MTT assay.  It was found that the derivatives were more active against HeLa than MCF-7.  The results also indicated that 4-methoxy group is the synergistic group of paeonol’s anti-tumor activity and ketone carbonyl side chain is essential functional group of paeonol’s anti-tumor activity.  Compound 2d had stronger antiproliferative activities than paeonol against HeLa and MCF-7 cell lines with IC₅₀ values of 2.67 and 4.74 μmol·L⁻¹ respectively.  The results showed that paeonol derivatives were worth to be intensively studied further.