With the evolution of nanomedicine, the past decades witnessed diversified nanomaterials as marvelous anti-tumor tools ushering in a new era of tumor diagnosis and treatment. Among them, two-dimensional layered nanomaterial as an emerging class of nanomaterials has one dimension less than 100 nm, showing a high specific area and the thinnest sheet-like structure (Liu S, Pan X, Liu H. Twodimensional nanomaterials for photothermal therapy. Angew Chem Int Ed 2020;59:5890–900). The discovery of graphene drove the exploration of various new two-dimensional layered nanomaterials for tumor diagnosis and treatment including graphene-based nanomaterials, black phosphorus (BP), transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and bismuth oxyhalides (BiOX, X=F, Cl, Br, I) (Ma H, Xue MQ. Recent advances in the photothermal applications of two-dimensional nanomaterial: photothermal therapy and beyond. J Mater Chem 2021;9:17569). On the one hand, they exhibit strong near-infrared (NIR) absorption and the capacity of optimizing corresponding properties by adjusting the crystal structure. On the other hand, they own unique strengths such as fantastic physicochemical properties (graphene-based nanomaterials), high loading capacity (BP), distinct phase-dependent optical properties (TMDs), a specific chemical response to the tumor microenvironment (LDHs), and large X-ray attenuation coefficient (BiOX). Herein, we briefly introduce three typical two-dimensional layered nanomaterials, their prospects and future research priorities in tumor diagnosis and treatment are concluded.