BACKGROUND The aim of this study was to examine the association between serum expression of miRNA-155 and postoperative cognitive dysfunction (POCD) after laparoscopic surgery for colon cancer. MATERIAL AND METHODS We enrolled 110 patients scheduled to undergo colon tumor resection via laparotomy in Ningbo No. 2 Hospital from July 2013 to November 2015. The blood samples were collected from the participants 1 day before surgery. Multiple logistic regression analysis was used for the analysis of independent predictive biomarkers for POCD. RESULTS On the 7th postoperative day, 29 of the 110 participants developed POCD, yielding a POCD incidence of 26.4%. Age, MMSE score, duration of surgery and anesthesia, serum levels of CRP, TNF-α, urea, creatinine, and miRNA-155 were highly associated with the occurrence of POCD. Serum expression of miRNA-155 was shown by multiple logistic regression analysis to be an independent predictive indicator for POCD after surgery (OR: 2.732; 95%CI 1.415-5.233; P=0.002). CONCLUSIONS The serum expression of miRNA-155 is an independent predictive factor for POCD after laparoscopic surgery for colon cancer.