Cancer remains a great challenge for mankind. The complex and diverse phenotypes, mechanisms, as well as therapeutic responsiveness of cancer have gradually been understood since the second half of the 20th century, which was a representative of entering the molecular era of oncology research. In 2000, the groundbreaking review “Hallmarks of Cancer” came out and it had been updated to the third version with 14 characteristics of cancer in 2022. These series of reviews helped to distil the increasingly complicated concepts of oncology into a logical science, which contributed to a more comprehensive understanding of the mechanisms for cancer genesis and development and applying the knowledges to the diagnosis and treatment of tumors. Mastering, applying, and exploring the hallmarks of cancer will help us face the challenges of cancer more confidently in the future.