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Design of the Texas Hepatocellular Carcinoma Consortium Cohort Study. OBJECTIVES: The Texas Hepatocellular Carcinoma Consortium cohort study investigates risk factors of hepatocellular carcinoma (HCC) and biomarkers for early HCC detection in patients with liver cirrhosis. METHODS: Adult patients with liver cirrhosis are enrolled at 5 clinical centers from 3 cities in Texas, with a target of 5,000 patients. Clinical history, risk factor questionnaires, liver imaging, laboratory data, and blood samples were collected at enrollment and at each 6-month follow-up visit. RESULTS: The primary outcome was the development of HCC. Biomarkers were tested in banked blood samples using prospective specimen collection, retrospective blinded evaluation design. CONCLUSIONS: We describe study design, eligibility criteria, recruitment, study cores, and sample size and analysis considerations.