INTRODUCTION: Cytokine-release syndrome (CRS) in COVID-19 patients can cause multiorgan failure and higher mortality. We used a structured protocol based on clinical, biochemical, and interleukin 6 (IL-6) criteria for the identification of the subset of patients with CRS and analyzed the use of tocilizumab for their treatment. MATERIALS AND METHODS: We did a retrospective case-control analysis of all COVID-19 patients between 15 March and 15 May 2020 with severe to critical disease in ICU. They were evaluated for CRS, and 22 patients who met the criterion were given tocilizumab. The primary objective was to evaluate the effect of tocilizumab on escalation of respiratory support and ICU mortality. The secondary objectives were ICU length of stay, trends of inflammatory markers, and any adverse effects. RESULTS: The need for escalation of respiratory support was significantly lower in the tocilizumab group as compared to standard treatment ( = 0.001). The mortality at day 7 and 28 was also significantly lower in the tocilizumab group ( = 0.007 and = 0.001 respectively). There was a significant reduction in C-reactive protein (CRP) who received tocilizumab ( = 0.033). CONCLUSION: In our limited number of patients, timely intervention with tocilizumab in COVID-19 patients with CRS significantly improved overall ICU outcome by reducing the need for invasive ventilation and mortality. HOW TO CITE THIS ARTICLE: Nasa P, Singh A, Upadhyay S, Bagadia S, Polumuru S, Shrivastava PK, Tocilizumab Use in COVID-19 Cytokine-release Syndrome: Retrospective Study of Two Centers. Indian J Crit Care Med 2020;24(9):771-776.