Ulcerative colitis is a painful inflammatory disease that is associated with an increased risk of colorectal cancer, but the mechanisms linking these diseases are not well understood. There is mounting evidence that the receptor TLR4 (Toll like receptor 4) is a key bridge molecule linking the two. TLR4 is the receptor for endotoxins from gram-negative bacteria, including colitis-associated pathogens. This receptor is overexpressed in both colitis and colitis-associated cancer and may promote tumorigenesis by facilitating cell proliferation and protecting malignant cells against apoptosis. It may also accelerate invasion and metastasis while helping create a tumor-favoring microenvironment. More recently, research has suggested that the microRNA miR-155 may also play a role. The expression changes and cancer promoting properties of miR-155 in colitis-associated cancer development mirror those of TLR4. In other cell lines and disorders, there is evidence of interplay between miR-155 and TLR4, suggesting that miR-155 and TLR4 can form a positive feedback loop with miR-155 augmenting TLR4 signaling via negative regulators and TLR4 inducing miR-155 expression. While research confirming and examining this interaction in the context of colitis-associated cancer is needed, these pathways could be leveraged to develop novel treatments or prevention methods.