Abstract: Proteomics research has been performed for more than 20 years. Early research was based on simple Western blot technology, and later, mass spectrometry was used to identify proteins. However, the limited sequencing depth and the number of identified proteins in initial mass spectrometry technology have caused bottlenecks in proteomics research. In recent years, with the rapid development of mass spectrometry technology, high-throughput proteomics identification has been achieved, and proteomics research has entered a new era. At present, the application of high-throughput proteomics technology in the field of cancer mainly includes revealing the mechanism of tumorigenesis and development, searching for specific biomarkers, elucidating the mechanism of drug resistance, and identifying new therapeutic targets. Early detection and diagnosis of tumors are helpful for timely medical intervention, greatly improving the survival rate and quality of life. Recently, several candidate tumor biomarkers have been identified, but only a few have been used clinically. Here, aiming to explore tumor-specific biomarkers, we selected four high morbidity/mortality rate tumors with extensive application of high-throughput proteomics technology, such as lung, breast, colorectal, and liver cancer. We screened recently published studies from journals with high impact factors, evaluated by their expanded sample size or functional verification, and strong evidence in different tumor types. This article first briefly introduces mass spectrometry-based high-throughput proteomics technology and commonly used specimen types, and then focuses on reviewing the protein markers that may be used for early diagnosis, prognosis, and targeted therapy in the above four high-incidence cancers, aiming to provide a new theoretical basis for accurate diagnosis and treatment of tumors.