The nanomaterials with enzyme-like catalytic activity, named as nanozymes, have aroused wide research interest owing to their striking merits. Metal-organic frameworks (MOFs) have showed great prospect in the construction of novel nanozymes. In this review, firstly, we summarize the most recent contributions in the design construction of the MOFs-based nanozymes. Then, we concentrate our attention on their applications in the fields of sensing and cancer therapies. According to the design strategies, we categorized MOFs-based nanozymes into four classes for review (i.e. pristine MOFs, MOFs with modification, MOFs-based nanocomposites, and MOF derivatives). Meanwhile, the emerging and fascinating 2D MOFs-based nanozymes were also reviewed. A variety of novel applications are also discussed, including nanozymes catalytic mediated signal amplification in sensing applications (e.g. colorimetric sensing, fluorescent sensing, chemiluminescent sensing, electrochemical sensing, and surface-enhanced Raman scattering (SERS)), and nanozymes catalytic mediated cancer therapy (i.e. cancer-starvation therapy, enhancing photodynamic therapy, and cancer-starvation and PDT synergistic therapy). At the end of the article, future opportunities and challenges in this promising research area are tentatively proposed.