Third-order nonlinear optical phenomena lie at the heart of all-optical signal processing, where laser pulses are used to switch, modulate, or gate another laser pulse. Here we report that the solidified silk film possesses extremely large third-order susceptibilities (similar to 10(-9) esu) in a wide near-infrared spectral region. The nonlinearity of silk protein can be substantially enhanced by inducing stronger molecular interactions from van der Waals forces and hydrogen bonding. The biocompatibility and capability of nanofabrication techniques will enable us to pave new ways for nonlinear bioimaging and biosensing applications. (C) 2016 Optical Society of Americ