Objective: Coronavirus disease 2019 (COVID-19) is rapidly spread throughout the world and has resulted in considerable morbidity and mortality. Recent evidence shown that inflammatory burden and cardiac injury were commonly observed in these cases and strongly linked to mortality. However, the association between the pro-inflammatory cytokines and cardiac injury among critically ill patients with COVID-19 remains unknown. Therefore, the primary aim of this study is to elucidate the association between pro-inflammatory cytokines and cardiac injury for guiding therapy and reducing rising mortality of critically ill patients with COVID-19. Design: This single-center, retrospective, observational study was designed based on the critically ill patients with COVID-19 at Tongji Hospital of Huazhong University of Science and Technology, Wuhan, China, from February 1, 2020, to March 10, 2020. A total of 212 individuals aged > 42 years was confirmed to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and then enrolled in the study. Methods: Demographics and baseline clinical characteristics as well as laboratory examinations on admission were collected from the electronic medical records and analyzed between the patients with cardiac injury and without cardiac injury defined as the serum high-sensitivity troponin I (hs-cTnI) level above 99th percentile of upper reference limit. Logistic regression analyses were employed to predict risk factors related to cardiac injury. Results: Eligible patients (n = 212) were categorized into the cardiac injury group (n = 89, 41.9%) and the non-cardiac injury group (n = 123, 58.1%). The median age was 66 years, ranging from 42 to 92 years, and the majority of patients were 109 (51.4%) female. Cardiovascular comorbidities were frequent in these patients, hypertension was the most common in 97 (45.8%) patients, followed by diabetes 34 (16.0%) and coronary heart disease 23 (10.8%). Moreover, these cases with cardiac injury were significantly older ( P < 0.001), and tended to have significantly elevated leukocyte counts, as well as dramatically increased concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein, tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, IL-8, and IL-10 (all P < 0.05), but generally lower lymphocyte counts compared with those without cardiac injury ( P = 0.005). Stepwise logistic regression analysis showed that TNF-α [odds ratio ( OR ) 1.117, 95% confidence interval ( CI ) 1.032-1.210, P = 0.006], IL-2R ( OR 0.999, 95% CI 0.999-0.999, P = 0.026), IL-8 ( OR 0.985, 95% CI 0.977-0.994, P = 0.001) were independent risk factors for the cardiac injury in critically ill patients with COVID-19. Conclusion: Pro-inflammatory cytokines are associated with cardiac injury, which indicated hyper-inflammatory response may highly involve in cardiac injury among critically ill patients with COVID-19. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was conducted in accordance with the principles of the declaration of the National Health Commission of China and approved by the Research Ethics Commission of Renmin Hospital of Wuhan University (Approval number WDRY2020-K061) and written informed consent was waived by the Ethics Commission of the designated hospital for patients due to the rapid emergence of this infectious disease.