Objective To explore the alteration of nuclear matrix proteins and the configurational changes of nuclear matrix (NM) system during differentiation of the osteosarcoma MG-63 cells EM>in vitro/EM> after being induced by the combination of ginsenoside Rg1, cinnamic acid and tanshinoneⅡA (RCT). Methods Cell cycle was investigated by flow cytometry and the growth curve was drawn with MTT method. The cells treated with or without RCT were subjected to selective extraction method and prepared for whole mount electron microscopy observation. The nuclear matrixintermediate samples were examined under light and transmission electron microscopes respectively. The nuclear matrix proteins were subjected to analysis of proteomic technique. Results The proliferstion of the MG-63 cells treated with RCT were repressed markedly; the rate of repression was 72.37％ on the seventh day，and the cell cycle was blocked at G0/G1 phase. The typical malignant phenotype of nuclear matrix of MG-63 tumor cell were reversed to normal cells. The expression of many functional proteins of nuclear matrix were changed in the MG-63 cells after the treatment with RCT. Conclusion RCT can repress markedly the proliferation of MG-63 cells, block cell cycle, induce a restorational change to the nuclear matrix architecture similar to that of normal cells, and change the const