Background: Porcupine bezoar, a phytobezoar used as traditional medicine, was recently claimed to effectively treat cancer. However, there is a lack of scientific evidence to prove the claim. Objectives: This study aimed to scientifically examine porcupine bezoars as a potential anticancer agent and to investigate their principal bioactive constituents. Materials and Methods: The porcupine bezoars were extracted using methanol and further Sephadex LH-20 column chromatography was used to enrich the tannins content. The inhibitory effects of the crude extracts on a panel of cancer cell lines were first determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Then, the anticancer activities of the enriched fractions in selected cell lines were analyzed, while the chemical composition of the active fraction was identified using liquid chromatography––electrospray ionization-tandem mass spectrometry. Results: Crude extracts of black date and powdery date effectively inhibited colon cancer cell lines HT-29 and HT-116, but not the normal colon cells, and their tannin-enriched fractions demonstrated higher inhibitory effects when compared to the extracts. Further, the fractions arrested cell cycle at S phase and induced apoptosis in treated colon cancer cells with a similar effect to that of commercial tannic acid. Lipoxygenase activity which plays a role in tumorigenesis of colon cancer was also inhibited by these fractions. Chemical analysis found that both the enriched fractions and commercial tannic acid share similar chemical constituents, including gallic acid and its derivatives (polygalloyl glucose). Conclusion: Together, the results suggest that tannic acid in porcupine bezoars may inhibit colon cancer cells by interfering cell proliferation and triggering program cell death in the cells.