Objective To discuss the relationship between antibiotic prophylaxis and surgical site infection (SSI) in colorectal cancer. Methods A survey of 880 patients with colorectal cancer from Jan. 1998 to Dec. 2008 were studied. Patients were divided into two groups by antibiotic duration: ≥24 h group (n=401) and lt;24 h group (n=479). To compare the differences of surgical site infection between two groups. Results For SSI patients, operation time obviously prolonged (P=0.04), or with more blood loss (P=0.03) and longer time use of antibiotics (P=0.04). In colon cancer patients with SSI operation time was significantly different from the cases of colon cancer without SSI （P=0.01）, while there was no difference between SSI and operation time, blood loss and duration of antibiotics （Pgt;0.05）. Conclusion Longer operation time, more blood loss and longer bleeding time are the risk factors of surgical site infection. Moreover prolonged antibiotic prophylaxis can not decrease the incidence of SSI.