Bcl-2 is a prominent member of the Bcl-2 family of proteins that regulate the induction of apoptosis. Here, we investigated the effect of Bcl-2 small interfering RNA (siRNA) combined with miR-15a oligonucleotides (ODN) on the growth of Raji cells. The expression levels of Bcl-2 mRNA and protein were detected. The inhibition of cell growth and apoptosis was determined. Atomic force microscopy was utilized to observe the cell-surface ultrastructural changes. After transfection of combination, protein and mRNA levels of Bcl-2 obviously were decreased. The growth of cells was significantly inhibited compared with those cells transfected with Bcl-2 siRNA or miR-15a alone. Apoptotic rate significantly increased. The cells of apoptosis showed a roughness variation on cell membranes. These results suggest that the combination of Bcl-2 siRNA and miR-15a ODN increases apoptosis in Raji cells. Our study implies that the combination of Bcl-2 siRNA and miR-15a may be a useful approach in treatment for lymphoma.