Abstract: OBJECTIVE To study the release and anti-tumor effect of curcumin derivatives, mPEG_2k-Gly-Cur, mPEG_2k-Gly-Cur-OA and Cur-OA₂，in vitro. METHODS The release property of curcumin derivatives in HepG2 cell culture supernatant was studied by HPLC method; furthermore, the antitumor activity of the derivatives in vitro was evaluated by MTT method with HepG2 cell lines. RESULTS HPLC detection conditions of curcumin were established. In deactivated cell culture supernatant, mPEG_2k-Gly-Cur and mPEG_2k-Gly-Cur-OA could release curcumin in a rational speed, while the release speed of Cur-OA₂ was too slow to be able to show any potential application, however, the release rate of curcumin from Cur-OA₂ and other curcumin derivatives was remarkably promoted in the untreated HepG2 cell culture supernatant, which may imply enzyme hydrolysis takes place. Additionally, MTT assay confirmed that three derivatives still had cell growth inhibition activity against HepG2 cell lines, and the derivative Cur-OA₂ with the strongest activity, but all were less efficient than curcumin. CONCLUSION Curcumin stability can be effectively improved after modification and the oleic acid double esterification derivative may enhance anti-hepatic carcinoma activity by cell phagocytize way, which deserves further research.