Few studies reported the risk factors of fatal outcome of hospitalized patients with coronavirus disease 2019 (COVID-19). We aimed to identify the independent risk factors associated with fatal outcome of hospitalized COVID-19 patients.The clinical data of 109 consecutive COVID-19 patients including 40 (36.7%) common cases and 69 (63.3%) severe cases were included and analyzed.Multivariate regression analysis indicated that platelets (PLT, OR, 0.988; 95% CI, 0.978-0.998; P=0.017) and C-reactive protein (CRP) (OR, 1.047; 95% CI, 1.026-1.068; P<0.001) levels were the independent risk factors of fatal outcome in COVID-19 patients. The optimal cut-off value of PLT counts for predicting fatal outcome was 161x109/L with the area under receiver operating characteristic curve (AUROC) of 0.824 (95% CI, 0.739-0.890). The optimal cut-off value of CRP for the prediction of fatal outcome was 46.2 mg/L with the AUROC of 0.954 (95% CI, 0.896-0.985). The CRP levels had higher predictive values for fatal outcome than PLT (P=0.016). The cumulative survival rate was significantly higher in patients with PLT>161x109/L compared with patients with PLT≤161x109/L (89.4% vs. 12.5%, log-rank test X2=72.17; P<0.001). Survival rate of COVID-19 patients was prominently higher in CRP≤46.2 mg/L patients compared with patients with CRP>46.2 mg/L (95.9% vs. 22.9%, log-rank test X2=77.85; P<0.001).PLT counts and CRP levels could predict fatal outcome of hospitalized COVID-19 patients with relatively high accuracy.