A hydrostatic high pressure cell is used to record pressure resolved wide-angle X-ray microdiffraction data (WAXS) from Bombyx mori silkworm silk fibers with in situ pressurization in the range of 0.010.5 GPa (0.15 kbar). From the pressure dependent peak positions of (002), (020), (200), and (210) Bragg reflections the (anisotropic) elastic moduli of compression were determined for the different unit cell axes of the crystalline fraction of silk fibroin, comprising of stacked polyalanine beta-sheets. The data are compared with X-ray diffraction results previously obtained from silkworm silk at tensile load and spider silk data at high hydrostatic pressure and indicate a different response of the silk fibroin structure to pressure versus tensile load. The response of the unit cell of silkworm silk fibroin to the applied pressure is discussed and modeled taking into account the weak van der Waals bonds between protein beta-sheets. Differences are pointed out between the responses of silks nanostructure to unidirectional (tensile) load versus the undirected pressure load. Next to the direct determination of the elastic moduli for the different crystal lattice parameters the pressure response of what is usually referred to as the amorphous phase is also considered.