Objectives: Association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and kidney injury has been noted in previous studies. However, the mechanisms remain unknown. The present study aimed to explore the potential mechanisms of kidney injury in COVID-19. Methods: Demographic characteristics, underlying diseases, signs, symptoms, and laboratory data of 100 COVID-19 patients were collected and analyzed in this retrospective study. Patients were divided into three groups: mild, moderate, and severe to critical group. Kidney injury was evaluated by markers including estimated glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen, and cystatin C. Results: A total of 100 patients with 12 mild, 63 moderate, and 25 severe to critical COVID-19 were included in this study. The kidney injury markers including eGFR, serum creatinine, blood urea nitrogen, and cystatin C all worsened significantly with an increase in disease severity. The correlation test showed that cytokines IL-2R, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha were statistically correlated with eGFR and cystatin C. In multivariate analysis, log IL-6 (beta = 0.331, p = .001 for eGFR and beta = 0.405, p < .001 for cystatin C) and log TNF-alpha (beta = -0.316, p = .001 for eGFR and beta = 0.534, p < .001 for cystatin C) were found to be the major independent predictors of kidney injury. Conclusion: Serum IL-6 and TNF-alpha levels were the major independent predictors of kidney injury in COVID-19.