Despite great progress in synthesis and application of graphene-like materials, it remains a considerable challenge to prepare two-dimensional (2D) nanostructures of nonlayered materials that may bring us surprising physical and chemical properties. Here, we propose a general strategy for the growth of 2D nonlayered materials by van der Waals epitaxy (vdWE) growth with two conditions: (1) the nonlayered materials satisfy 2D anisotropic growth and (2) the growth is implemented on the van der Waals substrates. Large-scale ultrathin 2D Pb_1–xSn_xSe nanoplates (∼15–45 nm) have been produced on mica sheets by applying this strategy. Benefiting from the 2D geometry of Pb_1–xSn_xSe nanoplates and the flexibility of mica sheet, flexible photodetectors that exhibit fast, reversible, and stable photoresponse and broad spectra detection ranging from UV to infrared light (375, 473, 632, 800, and 980 nm) are in situ fabricated based on Pb_1–xSn_xSe nanoplates. We anticipate that more nonlayered materials will be developed into 2D nanostructures through vdWE, enabling the exploitation of novel electronic and optoelectronic devices.