Deoxyribose nucleic acid (DNA), a type of soft matter, is often considered a promising building block to fabricate and investigate hybrid heterostructures with exotic functionalities. However, at this stage, investigations on DNA-enabled nanoelectronics have been largely limited to zero-dimensional (0D) and/or one-dimensional (1D) structures. Exploring their potential in higher dimensions, particularly in combination with hard matter solids such as van der Waals (vdW) two-dimensional (2D) materials, has proven challenging. Here, we show that 2D tessellations of DNA origami thin films, with a lateral size over 10 μm, can function as a sufficiently stiff substrate (Young's modulus of ~4 GPa). We further demonstrate a two-dimensional soft-hard interface of matter (2D-SHIM), in which vdW layers are coupled to the 2D tessellations of DNA origami. In such 2D-SHIM, the DNA film can then serve as a superlattice due to its sub-100 nm sized pitch of the self-assemblies, which modulates the electronic states of the hybrid system. Our findings open up promising possibilities for manipulating the electronic properties in hard matter using soft matter as a super-structural tuning knob, which may find applications in next generation nanoelectronics.