Abstract: Background and Objectives: Plant and marine extracts remain popular subjects for drug development. Exploring the potential of endemic Philippine plants as sources of cytotoxic compounds, this study looked into the cytotoxicity of Garcinia rubra Merr. against selected human cancer cell lines. Materials and Methods: Sub-fractions from the ethyl acetate fraction of G. rubra leaf were generated using vacuum liquid chromatography. Cytotoxicity of the fractions against colorectal, breast and lung adenocarcinoma cell lines was assessed and the most toxic sub-fraction was screened for selected hallmarks of apoptosis. Its selectivity for cancer was then determined. Moreover, the potential of the most active sub-fraction to act in synergism with doxorubicin was assessed using combinatorial assay. Lastly, the phytochemical constituents of the sample were screened. Results: Fractions 6, 7, 8 and 9 were active against the cancer cell lines tested. Fraction 7 induced apoptosis against colorectal cancer cells, but was not selective against cancer cells. It also proved to act synergistically with doxorubicin, allowing even sub-lethal concentrations to induce cell death. Lastly, phytochemical screening showed that the active fraction contained condensed tannins and phenolic compounds. Conclusion: Garcinia rubra was established to be a good source of cytotoxic and pro-apoptotic compounds.