Abstract: Objective To observe the expression of transcription factor E3(TFE3) and cathepsin K(Cath-K) in Xp11.2 translocation renal cell carcinoma. Methods Sixty-five cases renal cell carcinoma paraffin block specimens were collected from January 2006 to March 2013 at the Affiliated Drum Tower Hospital of Nanjing University Medical School that less than 45 years or pathology suspected Xp11.2 translocation renal cell carcinoma,TFE3 and Cath-K immunohistochemistry and fluorescence in situ hybridization (FISH) were detected.FISH positive was used to be diagnosis criteria of Xp11.2 translocation renal cell carcinoma,and to analyze TFE3 and Cath-K sensitivity,specificity,positive predictive value and negative predictive value in the diagnosis of Xp11.2 translocation renal cell carcinoma. Results TFE3 and Cath-K diagnosis Xp11.2 translocation renal cell carcinoma sensitivity were 95.5% and 72.7%,the specificity were 93.0% and 100%,the positive predictive value were 87.5% and 100%,negative predictive value were 97.6% and 87.8%.United TFE3 and Cath-K diagnosis Xp11.2 translocation renal cell carcinoma sensitivity was 94.1%,specificity was 100%,positive predictive value was 100%,negative predictive value was 98.0%. Conclusions Age,hematuria and tissue morphology remains were one of the indicators in diagnosis of Xp11.2 translocation renal cell carcinoma.TFE3 with a high sensitivity and negative predictive value,Cath-K with a high specificity and positive predictive value in diagnosis of Xp11.2 translocation renal cell carcinoma.Combined TFE3 and Cath-K can improve the accuracy diagnosis of Xp11.2 translocation renal cell carcinoma.