Qinba selenium mushroom is a mushroom belonging to the Basidiomycetes family, which is believed to have anti- oxidant, anti-tumoral and anti-mutagenic activities. However, the efficacy of Qinba selenium mushroom against multiple myeloma has not been confirmed. The present study aimed to investigate the apoptotic effect of FA-2-b-β, the selenium mushroom extract from Qinba on multiple myeloma (MM) cells. The MM RPMI-8226 cells were treated with FA-2-b-β at different concentrations and time points. MM RPMI-8226 cell proliferation and apoptosis were detected by the Cell Counting Kit-8 (CCK-8) assay and Annexin V/propidium iodide (PI) assay, RT-QPCR and western blotting analyses were performed to determine the proteins and pathways involved. The results of the present study demonstrated that FA-2-b-β has high anti-proliferative activities and strong pro-apoptotic effects on MM RPMI-8226 cells, and its pharmacological effects on proliferation changes occurred in a dose- and time-dependent manner. In addition, we found that FA-2-b-β was able to induce cell apoptosis and promote cell cycle arrest at G0/G1 phase. In summary, the results illustrate the involvement of FA-2-b-β in mediating G0/G1 cell cycle arrest and apoptosis in MM RPMI-8226 cells, which suggested that FA-2-b-β might have therapeutic potential against multiple myeloma as an effective compound, and may provide useful information for the development of a novel therapeutic target in this area.