Objective To observe the effect of curcumol on the biological behavior of multiple myeloma (MM) cells, thus studying its possible mechanisms for MM treatment. Methods Bone marrow mesenchymal stem cells (BMSCs) and multiple myeloma cell line 8226 (RPMI 8226) were taken as sub- jects, which were then divided into the RMPI 8226 group (cultured by RMPI 8226 alone) and the BMSCs + RMPI 8226 group (cultured by BMSCs and RMPI 8226). Curcumol in different concentrations (0. 1, 0.5, 1. 0 , 10.0 μg/mL) was added to cells in the two groups respectively. Cell proliferation, cell cycle, and ap' optosis induced by curcumol were examined by flow cytometry. The expressions of receptor activator of nuclear factor Kb ligand ( RANKL ) and osteoprotegerin ( OPG) were detected using reverse tran- scriptase-polymerase chain reaction (RT-PCR). Results Curcumol induced arrested cell cycle of RMPI 8226. The arrest of RMPI 8226 cell cycle was more obviously in the RMPI 8226 group than in the BMSCs + RMPI 8226 group. After curcumol treatment the cell proliferation of RPMI 8226 was significantly inhibited (P <0. 01) and its apoptosis was increased (P <0. 01). Co-cultured with BMSCs decreased curcumol in- duced apoptosis of RPMI 8226. Curcumol down-regulated the expression of osteogenic differentiation related gene RANKL, and up-regulated the expression of OPG. Conclusions Curcumol disturbed the cell cycle and induced apoptosis of RPMI 8226 cells. Curcumol up-regulated the expression of OPG as well as down-regulated the expression of RANKL. Co-culture with BMSCs could obviously inhibit curcumol in- duced apoptosis of MM cells, which might be associated with drug resistance of MM cells.