Background: In patients with colorectal cancer (CRC) the local and systemic inflammatory responses (LIR and SIR) are important determinants of disease progression. The present study examines the association of transcription factor RelB, a key member of the non-canonical NF-κB pathway and its association with LIR and SIR in patients undergoing resection of CRC. Methods: Patients with stage I-III CRC who underwent curative resection in a single institution and were in a previously constructed tissue microarray were studied. IHC was utilised to examine cytoplasmic and nuclear RelB expression. The relationship between RelB, clinicopathological characteristics, LIR (Klintrup-Mäkinen (KM) grade, CD3⁺ and CD8⁺T-cell density), SIR and cancer-specific survival (CSS) was examined. Results: 208 patients were included in the analysis. Cytoplasmic RelB (cyto-RelB) was associated with nuclear RelB (p=0.006). High expression of cyto-RelB was associated with MMR competence (p=0.010) but not with TNM stage (p=0.468), venous invasion (p=0.973), tumour budding (p=0.068), tumour necrosis (p=0.786), tumour cell proliferation (p=0.907), BRAF V600E mutation (p=0.585) or administration of adjuvant chemotherapy (p=0.853). High cyto-RelB was inversely associated with mGPS (mGPS >1: low cyto-RelB – 19% vs. high cyto-RelB – 8%, p=0.017). Also, cyto-RelB was inversely associated with tumour inflammatory cell infiltrate at the margin, Klintrup-Mäkinen grade (p=0.059), (CD3⁺p=0.010, CD8⁺p=0.007) and in the tumour (CD3⁺p=0.002) and a trend with tumour stroma percentage (p=0.079). High expression of cyto-RelB was not significantly associated with CSS (p=0.052). Conclusions: In patients undergoing CRC resection, high expression of cyto-RelB was associated with an adverse host local inflammatory response. Up-regulation of the non-canonical NF- κB pathway may be an important mechanism whereby the tumour deregulates local inflammatory responses and evades host immunosurveillance. Further investigation of inflammation based signal transduction pathways in patients with colorectal cancer is warranted.