<p>Crystalline grain refinement is a highly universal technique for increasing the strength of metals and alloys, and recent challenges have explored the possible application of such fine-structuring effects to various types of materials. Recently, a remarkable strengthening phenomenon has been found for a semi-crystalline polyethylene with a crystalline/amorphous lamellar structure, whose tensile strength is increased by an order of magnitude after applying the pre-heat-elongation (PHE) process. Here we provide a series of unambiguous evidences that such toughening is indeed due to nano-structuring and not to an increase in crystallinity, as is commonly used for semicrystalline polymers. Electron microscopy observations as well as X-ray diffraction experiments clearly show that the PHE process introduces a remarkable ultrafine-mosaic (~10 nm) into the crystalline lamellae. Ultralarge-scale molecular dynamics simulations provide further insights at the molecular level that chain spreading leads to the development of nanocrystalline mosaics, where the amorphous tie-chains effectively bridge across the multiple nano-lamellae, thereby strengthening the polyethylene. We show that a crystalline-size effect on strength can be well described by the Hall-Petch type relationship of size-inverse dependence, a well-known empirical rule for strengthening metals/alloys, providing a novel strength-ductility tailoring method based on higher-order structure control (i.e., crystalline-size control) of semi-crystalline polymers.</p>