The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated forty-three adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). Comparison of the haematological parameters between the mild and severe groups showed significant differences in IL-6, D-Dimer, GLU, TT, FIB and CRP (P <0.05). The optimal threshold and area under the ROC curve of IL-6 were 24.3 pg/mL and 0.795 respectively, while those of D-Dimer were 0.28 microg/L and 0.750, respectively. The area under the ROC curve (AUC) of IL-6 combined with D-Dimer was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and D-Dimer tandem testing was up to 93.3%, while the sensitivity of IL-6 and D-Dimer by parallel test in the severe COVID-19 was 96.4%. IL-6 and D-Dimer were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value. This article is protected by copyright.