Cancer, which is a leading cause of deaths around the world, is characterized by genetic mutations and epigenetic changes. Baicalin and its aglycone baicalein, the major bioactive flavones derived from the dried root of Scutellaria baicalensis Georigi, belong to flavonoid compounds. Many studies demonstrated that both of them exhibited remarkable promising anticancer activities. This study summarized potential anticancer mechanisms of baicalin and baicalein including induction of apoptosis, initiation of cell cycle arrest, suppression of metastasis, induction of autophagy, and regulation of immunity. Combination strategies involving baicalin or baicalein as chemotherapeutic adjuvants, clinical trial and safety were also discussed. In addition, we compared the difference in their anticancer effects. Interestingly, baicalein showed quicker and stronger inhibitory effects on multiple cancers than those of baicalin, probably due to its smaller size and high lipophilicity which contribute to fast absorption and improve ability to penetrate cells. Taken together, both baicalin and baicalein are effective in treating cancer with good tolerance. However, deglycosylation of baicalin to baicalein was found to have stronger anticancer potential.