Phenolic compounds are very important in the prevention and treatment of many civilization diseases, including colorectal cancer (CRC). In the present study we investigated and compared the phytochemical composition, antioxidant and cytotoxic activity of Japanese quince (Chaenomeles japonica L.) leaves crude phenolic extract (CPE) and purified phenolic-rich extracts (PRE). The UPLC-Q-TOF-MS analysis showed that both extracts contain diversified phenolics compounds (33 - 36 compounds in the PRE and CPE, respectively), among which chlorogenic acid and naringenin hexoside turned out to be the main constituents. Both FRAP and ABTS tests showed that PRE had 2-fold higher antioxidant activity compared to CPE. Furthermore, PRE exhibited a higher cytotoxic activity towards colon cancer cells (SW-480 and HT-29) than CPE. After 24-hours incubation with PRE the IC50 value for SW-480 cell line was obtained at the concentration of 239 μg/mL, while CPE treatment caused the same decrease only after 72h at 277 μg/mL. In addition, PRE had a stronger cytotoxic effect on the colon cancer cell lines (SW-480 and HT-29) than on normal intestinal cells (CCD-18Co and CCD 841 CoN). These results provide the first evidence that extracts from Japanese quince leaves (especially phenolic-rich extract, PRE) strongly decrease the viability of both SW-480 and HT-29 lines, which may suggest their cytotoxic activity towards colon cancer cells.