Objective To identify molecules in peripheral blood for the early diagnosis of hilar cholangiocarcinoma (HCCA).Methods Plasma samples were collected from patients with HCCA (n =30),primary choledocholithiasis (n =15) and choledochal cyst (n =15) as well as the healthy individuals (n =20).Small molecules in plasma metabolites were detected by the gas chromatography time-of-flight mass spectrometry (GC-TOF MS).The data of these blood samples were analyzed using multivariate analysis to create a model of differential diagnosis and screen the significant markers.Results We identified one specific plasma metabolite in HCCA,D-galacturonic acid.The average peak area was respectively 0.001 204 584,0.000 110 87,0,and 0.000 002 389 3 (mAu × min) in HCCA group,the healthy control group,choledochal cyst group and primary choledocholithiasis group respectively.D-galacturonic acid in HCCA group was significantly higher than in the healthy control group (P < 0.05),choledochal cyst group (P < 0.05) and primary choledocholithiasis group (P < 0.05).Conclusion Combined with multivariate statistical methods,we found metabolomics technology could provide a new method for the diagnosis of HCCA and a new way for the study of the pathogenesis. Key words: Metabolomics ; Klatskin's tumor ; Diagnosis