The aim of this study was to evaluate the effect of curcumin combined with Lactobacillus rhamnosus GG cell-free supernatant (LGG CFS) on the proliferation and induction of apoptosis in SCC-9 oral squamous cell carcinoma (OSCC) cells. Curcumin (40 µg/ml) and 25% v/v LGG CFS (108 CFU/ml), both alone and in a combination regimen, significantly decreased the viability of SCC-9 cells and normal human gingival fibroblast (HGF) cells. Interestingly, the combination of low doses of curcumin (5 µg/ml) and 25% v/v LGG CFS (106 CFU/ml) had no effect on the HGF cells but significantly inhibited the viability of SCC-9 cells (p < 0.05). Flow cytometric analysis revealed that SCC-9 cells treated with the combination of low-dose curcumin and low-dose LGG CFS had a higher apoptotic rate than the cells in the control group and the single treatment groups (p < 0.05). The combined treatment also significantly increased the Bax/Bcl2 mRNA and protein expression in SCC-9 cells (p < 0.05) but not in HGF cells, indicating the underlying mechanism of the combination regimen. There was no significant difference in caspase-3 protein expression or the Bcl-xL/Bak and Mcl-1/Bak ratios between the treatment and control groups in both cell lines. These findings suggested that the coadministration of curcumin and LGG could exhibit anticancer effects in SCC-9 cells without causing toxicity to normal fibroblast cells.