Breast cancer resistance protein (BCRP) protects tissues by actively transporting xenobiotics and their metabolites out of the cells. BCRP is expressed in the apical membrane of normal intestinal and colonic epithelium. The BCRP substrates include a number of structurally unrelated compounds, such as drugs, pesticides, carcinogens and endogenous compounds. Although the functional and common BCRP alleles, 34G>A and 421C>A, are shown to vary by ethnicity, their potential mechanism has not been adequately described with regards to affecting the susceptibility to colorectal cancer. The present study aimed to evaluate the effects of the BCRP variants on the susceptibility to colorectal cancer and to predict the individual responses to xenobiotics transferred by BCRP. BCRP 421C>A was significantly associated with the colorectal cancer risk (odds ratio, 16.12; P=0.005). These findings are the first results of BCRP allele distributions in the Turkish population and provide an understanding of the correlation between therapeutic approaches and etiology of colorectal cancer.