N6-methyladenosine (m 6 A) is the most abundant RNA modification. M 6 A RNA methylation is reversible: m 6 A is installed by "writers", removed by "erasers", and recognized by "readers". Readers are executors to regulate RNA metabolism by recognizing specific m 6 A sites, including RNA splicing, export, translation and decay. YTHDF2 is the first identified m 6 A reader protein. YTHDF2 interacts with m 6 A-containing transcripts to accelerate the degradation process and regulate various biological processes, such as viral infection, stem cell development and cancer progression. Although there are some reviews about m 6 A modification in physiological and pathological processes, few reviews focus on roles of YTHDF2 in cancers to date. Therefore, in this review, we attempted to systematically summarize m 6 A reader protein YTHDF2: its structure, mechanisms in regulating RNA metabolism, roles in cancer progression and potential application for cancer treatment, which might inspire new ideas for m 6 A research in cancers and provide novel insights into cancer treatment.