Background: The FIB-4 index, a noninvasive tool (FIB-4 index = age × aspartate transaminase (AST)/(platelet count × √alanine aminotransferase (ALT)), is a useful assessment for liver fibrosis. Patients with a high FIB-4 index were reported to have a high risk of developing hepatocellular carcinoma (HCC). This study analyzed the clinical association of the FIB-4 index with HCC development in patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD–CHB). Methods: This retrospective study analyzed 237 consecutive patients with NAFLD–CHB between January 2006 and December 2010 at the National Police Hospital in Korea. Patients with HCC at baseline and those diagnosed with HCC within 6 months from baseline were excluded. Propensity score matching analysis (PSM) was adopted to balance the baseline characteristics between patients with low and high FIB-4 index values. The cumulative rates of HCC development were compared between the two groups using the Kaplan–Meier method in the matched population. Results: The median follow-up duration was 13 years (interquartile range, 8.2–15.7). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, with an AUC of 0.70. Among a total of 237 patients with NAFLD–CHB, HCC developed in 20 patients (8.4%) (14 of the 90 patients with a high FIB-4 index vs. 6 of the 147 patients (4.1%) with a low FIB-4 index; log-rank p = 0.003). Patients with a high FIB-4 index had a significantly and independently higher risk of HCC than those with a low FIB-4 index (adjusted hazard ratio, 4.35; 95%; confidence interval, 1.42–13.24; log-rank test, p = 0.006). Conclusion: A high FIB-4 index (≥1.77) might be a useful marker for predicting the development of HCC in patients with NAFLD–CHB.