Morinda citrifolia, Citrus maxima, Cassia fistula, Momordica charantia and Murdannia iorifirmis were found to associate with low incidence of oral cancer. Objective: To investigate their lethal effect on oral squamous cell carcinoma cell line (HSC-4). Method: The plants were extracted with water and then lyophilized. HSC-4 cells were maintained in DMEM complete medium. Herbal extract diluted in medium was added into culture. No additioning and additioning of 5-FU were used as a negative and positive control, respectively. After 24 hours of treatment, growth inhibition was analyzed by MTT assay and DNA fragmentation was determined by TUNEL method. Result: The finding showed that Citrus maxima seed did not have proliferative and morphological effects on HSC-4 cells. Morinda citrifolia leaf, Morinda citrifolia fruit, Cassia fistula leaf, Momordica charantia fruit and Murdannia iorifirmis leaf inhibited cell proliferation with the IC50 of 0.42% (w/v), 0.78% (w/v), 0.34% (w/v), 0.27% (w/v) and 0.14% (w/v) respectively, compared to 3.125% (v/v) of positive controls. Apoptotic properties such as cell shrinkage, membrane blebbing and chromatin condensation were also observed after herbal treatment. Conclusion: Morinda citrifolia, Cassia fistula, Momordica charantia and Murdannia iorifirmis have a cytotoxic activity and can induce apoptosis in oral squamous cell carcinoma.