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Background: Liver disease (LD) is a common pathology worldwide. Many patients remain asymptomatic and undiagnosed. Colorectal cancer (CRC) is a prevalent neoplasm and a leading cause of cancer-related deaths globally. Multiple studies suggest that inflammation in the liver could drive the initiation of colorectal cancer., Methods: This five-year (2018-2022) case-control study included 274 patients diagnosed with CRC and adenomas at a community hospital in Houston, Texas. Each patient's medical record was reviewed for pre-existing LD, including steatosis, cirrhosis, primary biliary cirrhosis, and Hepatitis B and C infections. This study aims to investigate the association between LD and CRC risk and assess differences by gender, race, and ethnicity. The study cohort comprised 124 (45.3%) women and 150 (54.7%) men. Data were compared and analyzed using a Chi-squared test for independence and binomial logistic regression. A p-value of < 0.05 was considered statistically significant.  Results: Patients with LD had a two-fold increase in the odds of developing CRC compared to those without LD, in both univariate and multivariate analyses (OR 2.13 {95% CI 1.30-3.49}, p = 0.003 / OR 2.30 {95% CI 1.37-3.87}, p = 0.002, respectively). The chi-square test revealed that the association between CRC and LD was stronger in women than in men (p = 0.018 and p = 0.056, respectively)., Conclusion: Our study establishes a positive correlation between LD and CRC development, suggesting LD is a potential risk factor for CRC, particularly in women. Future research directions include exploring the underlying mechanisms of this association, evaluating the utility of early CRC screening in individuals with LD, and assessing the impact of interventions targeting LD on CRC incidence and mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Institute Committee, Houston Methodist Willowbrook Hospital issued approval PRO00037701. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aillaud-De-Uriarte et al.)