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Due to the features of strong heterogeneity, difficult early diagnosis, poor prognosis, and high fatality rate, hepatocellular carcinoma (HCC) has become an important disease which threatens the health of the Chinese population. Accurate early diagnosis is crucial to improving the success rate of liver cancer resection and reducing postoperative recurrence and metastasis, and its core is the screening and validation of biomarkers for early diagnosis. Isobaric tags for relative and absolute quantitation (iTRAQ) and stable isotope labeling with amino acids in cell culture are important parts of proteomics technology, and iTRAQ has become the most important technique in quantitative proteomics technology due to its advantages of high throughput, high quantitative accuracy, and no limitation by sample source. This article reviews the research advances in molecular mechanism of the development and progression of HCC and screening of markers, in order to establish a theoretical foundation for in-depth understanding of the molecular mechanisms of the development and progression of HCC and the development of new biomarkers.