Abstract: Objective To observe the effects of different anesthesia on the level of S100β protein and postoperative cognitive dysfunction(POCD) in elder patients undergoing colorectal cancer resection. Methods Total 50 patients undergoing colorectal cancer resection,age ≥ 65,ASAⅠ-Ⅱ,were randomly divided into observed group(n=25) and control group(n=25) according to anesthesia methods.The observed group received general anesthesia combined with epidural anesthesia,while the control group received general anesthesia only;the two groups were taken the same general anesthesia medication but different drug concentration and dose in the anesthesia maintenance.The levels of serum S100β protein in the two groups at different time point(T0:before anesthesia,T1:2 h after surgery,T2:24 h surgery,T3:48 h after surgery,T4:72 h after surgery) were tested;The MMSE score,incidence of POCD,anesthesia time,recovery time,time to extubation,the number of awaken restlessness,the dose of Ephedrine and additional Sufentanil during the surgery,and the incidence of intraoperative awareness at each time point were recorded. Results The incidence of POCD were higher in the two groups at T1,the difference between the two groups was not statistically significant(P>0.05).But the incidence of POCD was significant lower in the observation group at T2,T3,and T4(P<0.05).The S100βprotein level at T1 and T2 were significantly higher than that at T0 in the observed group(P<0.05),while the S100β protein level at T1-T4 was higher than that at T0 in the control group(P<0.05).The time to recovery of consciousness and time to extubation in the observed group was significantly shorter than those in the control group(P<0.05),the incidence of awaken restlessness in the observed group was significantly lower than that in the control group(P<0.05),and the amount of Ephedrine and additional Sufentanil dose of observed group was significantly less than that in the control group(P<0.05). Conclusion The general anesthesia combined with epidural anesthesia for elder patients with colorectal cancer resection can reduce anesthesia drug dose and the incidence of early POCD,improve the quality of anesthesia.The changes of S100β protein levels have certain significance in predicting the occurrence of early POCD.