Pyrotinib is a novel human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor (TKI). Previous studies of pyrotinib showed that it is mainly excreted through the gastrointestinal tract rather than the kidneys, with little effect on renal function. Here, we report a patient with HER2‐mutated nonsmall cell lung cancer who developed acute kidney injury (AKI) after receiving pyrotinib treatment. This case alerts clinicians to the adverse renal effects of HER2 TKIs, especially in patients with chronic kidney disease. However, tumor treatment should remain a priority in clinical practice. In this case, AKI induced by pyrotinib was reversible. Therefore, there is no need to restrict the use of HER2 TKIs due to concerns about possible nephrotoxicity.