The objective of this study was to assess the association between dietary patterns and risk of hepatocellular carcinoma (HCC) among US adults in a hospital-based case-control study. We analyzed data from 641 cases and 1002 controls recruited at The University of Texas MD Anderson Cancer Center during 2001–2018. Cases were patients with a pathologically or radiologically confirmed new diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck cancer. Cases and controls were frequency-matched by age and sex. Dietary patterns were identified by principal component analysis. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed using unconditional logistic regression with adjustment for major HCC risk factors, including hepatitis B virus and hepatitis C virus infection. A vegetable-based dietary pattern was inversely associated with HCC risk (highest compared with lowest tertile: OR 0.66, 95% CI 0.46–0.94). A Western diet pattern was directly associated with HCC risk (highest compared with lowest tertile: OR 1.79, 95% CI 1.19–2.69). These findings emphasize the potential role of dietary intake in HCC prevention and clinical management.