Two-dimensional transition metal dichalcogenides have attracted widespread attention in cancer theranostics due to their high specific surface area and excellent photothermal conversion properties. However, their dimensions and biodegradability have limited the exploration of the therapeutic properties of transition metal dichalcogenides. Herein, we explore the mechanism of the keratin α-helix-to-random coil transition, as an actuation mechanism for the controllable design and precise synthesis of two-dimension copper sulfide nanoflakes (CuS NFs) with high absorption in the NIR-II window. Upon mixing keratin and Cu2+, the hydrogen bonds that maintain the α-helix are broken by copper ions to form biuret coordination, while the structure of the α-helix is transformed into a random coil, providing a more scalable space for the growth of CuS NFs. The CuS NFs prepared in this way possess the great advantages of outstanding uniformity, size controllability, and biodegradability. Importantly, the CuS NFs in the NIR-II window show an excellent photothermal conversion efficiency (32.9%) and extraordinary photoacoustic signal. This work updates the fabrication of two-dimensional transition metal dichalcogenides and greatly enhances their competitiveness in the area of cancer theranostics in the NIR-II region, and provides significant theoretical and practical opportunities for the development of keratin using biomimetic synthesis.