The response surface methodology was employed to study the acid extraction of pectin from sweet potato residues. The effects of extraction temperature, extraction time, solution pH and liquid/solid ratio on yield and galacturonic acid content of pectin were investigated. Experimental data were fitted to quadratic polynomial models and analysed using appropriate statistical methods. The determined optimum conditions were extraction temperature 93 °C, extraction time 2.2 h, solution pH 1.7 and liquid/solid ratio (v/w) 30:1. Under these conditions, the experimental extraction yield and galacturonic acid content of pectin were 5.09% and 70.03% (w/w), which were in good agreement with predicted values, 5.08% and 69.40%, respectively. In addition, sweet potato pectin exhibited remarkable antiproliferation effects on human colon cancer cells HT-29 and human breast cancer cells Bcap-37 by 46.64% and 42.64% at 1.00 mg mL−1 separately, indicating that it could potentially be used as a natural supplement in functional foods.