Background In this study, we aimed to investigate whether FIB-4 index is useful in predicting mortality in patients with concurrent hematological malignancies and COVID-19. We also aimed to determine the optimal cut-off point for the prediction. Methods This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia. Consecutive sampling of adults with hematological malignancies and COVID-19 was performed between May 2020 and January 2021. COVID-19 screening test using the reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal samples were performed prior to hospitalization for chemotherapy. FIB-4 index is derived from [age (years) × AST (IU/L)]/[platelet count (109/L) × pALT (U/L)]. The primary outcome of this study is mortality, defined as clinically validated death/non-survivor during a 3-months (90 days) follow-up. Results There were a total of 70 patients with hematological malignancies and COVID-19 in this study. Median FIB-4 Index was higher in non-survivors (13.1 vs 1.02, p<0.001). FIB-4 index above 3.85 has a sensitivity of 79%, specificity of 84%, PLR of 5.27, and NLR of 0.32. The AUC was 0.849 95% CI 0.735-0.962, p<0.001. This cut-off point was associated with OR of 16.70 95% CI 4.07-66.67, p<0.001. In this study, a FIB-4 >3.85 confers to 80% posterior probability of mortality and FIB-4 <3.85 to 19% probability. FIB-4 >3.85 was associated with shorter time-to-mortality (HR 9.10 95% CI 2.99-27.65, p<0.001). Multivariate analysis indicated that FIB-4 >3.85 (HR 4.09 95% CI 1.32-12.70, p = 0.015) and CRP> 71.57 mg/L (HR 3.36 95% CI 1.08-10.50, p = 0.037) were independently associated with shorter time-to-mortality. Conclusion This study indicates that a FIB-4 index >3.85 was independent predictor of mortality in patients with hematological malignancies and COVID-19 infection.