Sickle cell disease, is a genetic disorder caused by a mutation in the HBB gene, affecting the β-globin and resulting in the formation of sickle hemoglobin. The disease can affect the kidney through various mechanisms, including vaso-occlusion, ischemia-reperfusion, endothelial dysfunction, and hemolysis-induced renal injury. This article describes the case of a 41-year-old woman with sickle cell disease who presented with a hemolytic crisis, developed acute kidney injury (AKI), 8 grams of proteinuria in 24 hours, and required renal support therapy. A renal biopsy was performed, revealing focal segmental glomerulosclerosis (FSGS), severe acute tubular necrosis, interstitial fibrosis with moderate tubular atrophy, and pigment casts. Thus, histochemistry was performed with a positive reaction for iron with evidence of intraluminal and cytoplasmic granular deposits in the proximal tubules compatible with hemosiderin and negative for hemoglobin. The case of this patient with sickle cell disease and AKI illustrates the importance of considering hemoglobin cast nephropathy as a potential cause.