Objective To investigate the expression and significance of hamartin and tuberin protein in angiomyolipoma of the kidney. Methods The expression of the above biomarkers was detected in 43 cases of normal renal tissues and 86 cases of angiomyolipoma of the kidney by immunochemical EnVision method. Results There was positive expression of hamartin and tuberin protein in all the 43 cases of normal renal tissues. While in 86 cases of angiomyolipoma of the kidney, the positive expression rate of hamartin was 81.25%, and that of tuberin was 93.75%. Conclusion Loss of expression of hamartin and tuberin protein may be associated with the occurrence of some cases of angiomyolipoma of the kidney, and the pathogenesis of sporadic angiomyolipoma of the kidney may be different from that of tuberous sclerosis complex (TSC)-associated type.