Room-temperature liquid metal has been widely used in flexible and stretchable sensors, focusing on embedding liquid metal in microchannels, liquid metal microdroplets formation, captive sensors, and liquid metal nanoparticles, etc. In this paper, a facile Eutectic Galium-Indium (EGaln) liquid-based microfluidic high-sensitivity, skin-mountable, and ultra-soft stretchable sensor is developed. It comprises Ecoflex microfluidic assembly filled with EGaln, which serves as the working fluid of the stretchable sensor. The lithography method is applied to achieve microfluidic channel. The microfluidic channel is optimized by using topology method and finite element analysis, making this device with high conformability and high stretchability. This method achieved an outstanding effect on elastomer-encapsulated strain gauge, which displays an approximately linear behavior with a gauge factor (GF). The GF could reach as high as 4.95 when the strain ultimately reached 550%. Applications of detection of the joints, fingers, and wrists has been conducted and showed excellent results. This work can further facilitate the exploration and potential realization of a functional liquid-state device technology with superior mechanical flexibility and conformability.