Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19 9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2 5 elevated biomarkers were at an increased risk of relapse compared to those with 0 1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1 1.72) or postoperatively (HR 1.54, 95% CI 1.23 1.92). Patients with 2 5 elevated biomarkers were also at an increased risk of death compared to those with 0 1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39 2.24) or postoperatively (HR 1.83, 95% CI 1.44 2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.