【Abstract】 Objective To discuss the appropriate administration of cephalosporins in renal failure patients. Methods We retrospectively analyzed 30 renal failure patients developing encephalopathic syndrome and electroencephalogram changes during the cephalosporins treatment (daily dose of 2-3g). Results In the 30 patients, 29 completely recovered from encephalopathy syndrome after discontinuing of the drug for 2-5 days, and one patient died. Twenty-two patients were treated with hemodialysis, 2 with peritoneal dialysis, and 5 patients used antiepileptic drugs. Electroencephalogram showed background of generalized slow waves with continuous bursts of moderate to high amplitude, or sharp and slow wave activity in 23 of the 27 patients. Conclusions Regular dose of cephalosporins treatment may have neurotoxicity in renal failure patients, probably resulting from blood-brain barrier change, low drug clearance and higher blood drug concentration. Therefore, we should adjust the dosage of cephalosporins based on creatinine clearance rate, and discontinue the drugs once unexplained encephalopathy appears.