With the increasing interest and demand for epidermal electronics, a strong interface between a sensor and a biological surface is essential, yet achieving such interface is still a challenge. Here, a calcium (Ca)-modified biocompatible silk fibroin as a strong adhesive for epidermal electronics is proposed and the physical principles behind its interfacial and adhesive properties are reported. A strong adhesive characteristic (>800 N m(-1)) is observed because of the increase in both viscoelastic property and mechanical interlocking through the incorporation of Ca ions. Furthermore, additional key characteristics of the Ca-modified silk: reusability, stretchability, biocompatibility, and conductivity, are reported. These characteristics enable a wide range of applications as demonstrated in four epidermal electronic systems: capacitive touch sensor, resistive strain sensor, hydrogel-based drug delivery, and electrocardiogram monitoring sensor. As a reusable, biocompatible, conductive, and strong adhesive with water-degradability, the Ca-modified silk adhesive is a promising candidate for the next-generation adhesive for epidermal biomedical sensors.