Polydimethylsiloxane (PDMS) has many desirable features for microfluidics applications, particularly in diagnostics and pharmaceuticals, but its hydrophobicity and the lack of a practical method for bonding PDMS layers limit its use. Moreover, the flexibility of PDMS causes unwanted deformation during use in some applications. Here, we report a simple method for solving these problems simultaneously using an electron beam (EB) or γ-rays, which are commonly used for sterilizing medical products. Simply by applying EB or γ-ray irradiation to stacked PDMS layers, we can not only bond the interfaces between the layers by forming Si–O–Si covalent bonds but also achieve long-lasting hydrophilization and sterilization of the internal microchannels and chambers, prevent nonspecific adsorption and absorption of hydrophobic small molecules, and enhance the mechanical strength of the material by converting bulk PDMS into a Si–O_x-rich (where x is 3 or 4) structure though crosslinking. Unlike the one-at-a-time plasma process, EBs and γ-rays can penetrate through many stacked layers of PDMS sealed in their final package, enabling batch modification and bonding. The method requires no chemical crosslinkers, adhesive agents, or fillers; hence, it does not undermine the advantages of PDMS such as ease of molding in soft lithography, biocompatibility, and optical transparency. Furthermore, bonding is achieved with high-throughput yield because it occurs after re-adjustable alignment. We demonstrate that this method is applicable in the mass production of 3D integrated PDMS microfluidic chips with some glass-like properties as well as for 3D structures with complex shapes that are difficult to fabricate with plastic or glass.