Human muscles are notably toughened or softened with specific inorganic ions. Inspired by this phenomenon, herein we report a simple strategy to endow hydrogels with comparable ion-responsive mechanical properties by treating the gels with different ionic solutions. Semi-crystalline poly(vinyl alcohol) hydrogels are chosen as examples to illustrate this concept. Similar to muscles, the mechanical property of hydrogels demonstrates strong dependence on both the nature and concentration of inorganic ions. Immersed at the same salt concentration, the hydrogels treated with different ionic solutions manifest a broad-range tunability in rigidity (Young’s modulus from 0.16 to 9.6 MPa), extensibility (elongation ratio from 100% to 570%), and toughness (fracture work from 0.82 to 35 MJ m). The mechanical property well follows the Hofmeister series, where the “salting-out” salts (kosmotropes) have a more pronounced effect on the reinforcement of the hydrogels. Besides, the hydrogels’ mechanical performance exhibits a positive correlation with the salt concentration. Furthermore, it is revealed both the polymer solubility from amorphous domains and polymer crystallinity from crystalline domains are significantly influenced by the ions, which synergistically contribute to the salt-responsive mechanical performance. Benefitting from this feature, the hydrogels have demonstrated promising industrial applications, including tunable tough engineering soft materials, anti-icing coatings, and soft electronic devices.[Figure not available: see fulltext.].