High temperature and pH modification could produce functional pectins. In this study, high temperature-modified (HTCP) and pH-modified (MCP) citrus pectins were prepared for studying their anti-tumor activities in eight cancer cell lines and a mouse Sarcoma-180 (S-180) tumor model. HTCP inhibited the proliferation of these cancer cells and induced a caspase-3-dependent cell apoptosis and cell cycle arrest at G2/M phase. It also inhibited the growth of S-180 tumor to 49% of the control at the dose of 200 mg kg(-1) d(-1) and extended the survival time of the tumor-bearing mice. MCP had no anti-proliferative effects on these cancer cells and no anti-tumor effect in the mouse model. The anti-tumor activity of HTCP in the mouse tumor model was not correlated with immunomodulation and galectin-3 inhibition, but correlated well with proliferation inhibition. HTCP might be exploited as a functional food for cancer prevention and/or treatment.