Abstract Background and Aims The effects of hospital-acquired acute kidney injury (HA-AKI) on kidney cancer remain unclear. The study aimed to investigate the association between HA-AKI and kidney cancer by a large multicenter cohort study. Method The real-world cohort study included Chinese adults with at least two serum creatinine (SCr) tests within 7 days during hospitalization from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥26.5 μmol/l increase in serum creatinine concentration within 48 hours or a ≥50% increase over the baseline within 7 days. The primary outcome was a new diagnosis of kidney cancer, while the secondary outcomes included death attributed to kidney cancer and new diagnoses of other cancers of the urinary system. The Cox proportional hazard model was employed for analyses. Results Of the 342861 patients (median age, 57.06 [43.68, 68.54] yr; men, 179096 [52.2%]), 9337 patients experienced HA-AKI. During a mean follow-up of 2.03 years, 195 (0.57‰) patients with a new diagnosis of kidney cancer were detected. After multivariable adjustment, HA-AKI was significantly associated with a higher risk of kidney cancer (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.37-4.17, P = 0.003) and kidney cancer-specific death (adjusted HR, 3.19; 95% CI, 1.90-5.37, P < 0.001). We also found that relationships between HA-AKI and cancers of the urinary system, excluding kidney cancer, such as bladder cancer, prostate cancer, were not statistically significant. Conclusion HA-AKI was significantly associated with increased risk of kidney cancer and death attributed to kidney cancer. Our findings highlight the importance of monitoring HA-AKI patients for early detection of kidney cancer.