αA- and αB-crystallins, the major lens structure proteins and members of the small heat-shock proteins (sHSPs) family, play essential roles in maintaining normal cellular structure and physiology of both ocular and some non-ocular tissues. Mutations and abnormal expression of these sHSPs are associated with various human diseases such as cataract, neural disorders, and cardiovascular diseases. In addition, recent studies have revealed that the abnormal expressions and functions of both α-crystallins are associated with several types of tumors. In this regard, αA- and αB-crystallins seem to function differentially or even oppositely during tumorigenesis, and diverse molecular mechanisms have been proposed to explain their roles in cell apoptosis, cell proliferation and tumor metastasis. In this review, we have summarized the current status regarding the expression patterns and functions of αA- and αB-crystallins implicated in tumorigenesis, and discussed the possible mechanisms underlying their functions.