Background: To investigate the prognostic value of a novel immune-inflammatory index, the interleukin-6-tolymphocyte ratio (IL-6/LY), with the clinical outcomes of severe coronavirus disease 2019 (COVID-19) cases. Methods: A cohort study of COVID-19 patients in Tongji Hospital, from January 2020 to February 2020, was evaluated. Kaplan-Meier method and the log-rank test was performed to analyze survival data. Univariate and multivariate analyses were performed with COX proportional hazard regression model. The primary and secondary outcomes were in-hospital mortality and multiple organ dysfunction syndrome (MODS), respectively. Results: Total 320 adult patients were enrolled in our analyses. Patients were divided into low IL-6/LY group and high IL-6/LY group based on the cutoff value with 2.50. The Kaplan-Meier survival curves showed that highvalue group (IL-6/LY >= 2.50) had a greater risk of poor prognosis (P < 0.001, respectively). Multivariate analysis indicated that IL-6/LY was the independent risk predictor for in-hospital mortality (hazard ratio [HR], 3.404; 95% confidence interval [CI], 1.090-10.633, P = 0.035) and MODS development (HR, 4.143; 95%CI, 1.321-12.986, P = 0.015). Meanwhile, IL-6/LY was positively correlated with the MuLBSTA score (r = 0.137, P = 0.031), suggesting that IL-6/LY was associated with long-term mortality (90-day). Furthermore, kinetic analysis revealed that the dynamic changes of inflammatory immune indexes were related to the severity of the disease. Conclusions: The elevated IL-6/LY was related with the increased risk of poor prognosis. Not only that, IL-6/LY could be used for risk stratification and early clinical identification of high-risk patients.