Objective：To observe the morphological changes and analyze the differential protein spectrum of human malignant glioma cells SHG-44 after treated with Nordy （Chinese patent number：ZL02133700.4）, an analog of Nordihydroguaiaretic acid. Methods： The differentiation of SHG-44 cells was induced by 100μmol/L or 200 μmol/L Nordy; the morphological changes of cells were observed 24, 48 and 72 h after Nordy treatment and the findings were compared with those of the control group （received no treatment） . The total proteins were extracted from SHG-44 cells treated with 200 μmol/L Nordy for 72 h and cells in control group, then were subjected to two-dimensional gel electrophoresis. PDquest 7. 1 software was employed to compare the protein expression differences. The highly expressed differential proteins were identified by matrix-assisted laser desorption/ ionization-time of flight-mass spectrometry （MALDI-TOF-MS）. Results： The morphological changes of SHG-44 cells treated with 200 μmol/L Nordy were more obvious than those treated with 100 μmol/L Nordy, and the most obvious differentiation was found in the cells treated for 72 h. Compared with those of control group, 23 differential protein spots were identified by the two-dimensional electrophoresis, including 21 down-regulated ones and 2 up regulated ones. MALDI-TOF-MS showed that the highly expressed proteins were： an unknown protein, proliferation-associated gene A, Upl, alternative splicing factor ASF-3, cofilinl（non-muscle）, eukaryotic translation initiation factor 5A, beta galactoside binding lectin, and glutathione-S-transferase Pi. Conclusion.. Nordy can induce differentiation of human malignant glioma cells SHCr-44 in a time-effect and dose-effect dependent manner. The Nordy-induced differential proteins may function in multiple aspects such as cell proliferation, apoptosis and gene transcription