Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the 6th most common cancer-related death worldwide with 5-year relative survival of 20.3%. Although portal vein tumor thrombus is deemed as poor risk factor for HCC patients, the association of portal vein thrombosis (PVT) and HCC regarding inpatient mortality and morbidity outcomes is not well studied in hospitalized population. This study aimed to analyze the mortality, length of stay (LOS), and health care utilization in HCC patients with and without PVT. Methods: Nationwide Inpatient Sample (NIS) was queried to determine adult hospitalized patients with a primary diagnosis of HCC using ICD-10 codes. The primary outcome was defined as the effect of PVT on inpatient mortality in those patients. Secondary outcomes included LOS, total hospital charge, health care utilization, ICU admission. We evaluated the baseline characteristics using the t-test and chi-square test. Multivariable logistic regression analysis was performed to assess the association of HCC with PVT and inpatient mortality adjusted by age, gender, race, Charlson index, insurance, and household income. Results: A total of 10,205 HCC patients were identified, and 16.3% of these patients had PVT. HCC patients with PVT were younger (63.3 vs. 64.8 years, p < 0.001), more likely to be male (78.7% vs. 74%, p < 0.001), African American (20.3% vs. 15.8% p < 0.001), have low-income (p < 0.001) and more likely to have Medicaid insurance (23.8% vs. 19.1%, p < 0.001) compared to HCC patients without PVT. HCC with PVT had high Charlson Comorbidity index of > 7 (29.6% vs. 19.7%) (p < 0.001). The overall inpatient mortality rate was 8.1% for all patients who are admitted for HCC; higher in HCC with PVT (10.6%) vs HCC without PVT (7.6%) (p < 0.001). Age, Charlson index, African–American race found to be associated with inpatient mortality among hospitalized patients with HCC. HCC with PVT had a higher odds ratio with increased all-cause mortality of 43% compared to HCC without PVT (OR 1.43, 95% CI 1.19-1.72, p < 0.001), and the adjusted odds ratio was 1.25 (95% CI 1.03-1.52, p = 0.025). In addition, HCC with PVT was associated with increased LOS mean 6.3 vs. 5.6 days (adjusted difference: 0.5 p = 0.004), but total hospital charges were less in HCC patients with PVT (mean $75585 vs $91040, adjusted difference: $13437 p < 0.0001). There was no significant difference in ICU transfers and disposition. Conclusions: Hospitalized HCC patients with PVT have higher odds of inpatient mortality, LOS, and healthcare utilization than HCC patients without PVT. Age, higher Charlson index, African–American race were associated with inpatient mortality in HCC admissions. HCC with PVT should be identified and considered as a higher risk of mortality. Further efforts should be made to prolong survival, increase quality of life, and decrease hospital stay.