How the proteins are recognized and selectively degraded in the cellular life process is an important scientific question. The general mode of selective degradation of proteins in the cell in ATP- and ubiquitin-dependent pathway has been well studied. However, little attention has been directed toward the possible involvement of the proteasome in ubiquitin-independent proteolysis. In the past few years, many publications have provided evidence that the proteasome can degrade some proteins in a ubiquitin-independent manner. This pathway is involved in the elimination of some short-life regulated proteins, misfolded proteins, aged proteins and oxidized proteins as well as "quality control" of newly synthesized proteins, and involved in pathological processes such as cancer and neurodegenerative diseases. Therefore, it plays important roles in physiology and pathology. Some representative proteins degraded by the proteasome in a ubiquitin-independent manner in the past decade or two were summarized with focuses on their molecular mechanisms and the selected cases as examples to provide an overview of the field.