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Hepatocellular carcinoma (HCC) ranks fourth in cancer mortality worldwide, and third in China. Hepatitis B virus (HBV) infection is a main risk factor for HCC in China, and the early diagnosis of HCC in high-risk population is very important. However, the commonly used diagnostic biomarker alpha-fetoprotein has limitations in clinical practice. In order to identify reliable and noninvasive HCC urinary biomarkers, a high-throughput proteomics streamline was applied in the analysis of urine samples from 74 HCC and 82 high-risk patients with chronic HBV infected liver diseases. Candidate diagnostic markers were screened by feature selection algorithm, and were combined with random forest or simple voting algorithms in the training dataset. Then the multiple feature models were validated in an independent test dataset. The selected features were further verified by Multiple Reaction Monitoring (MRM) in another …