Microfluidics have attracted increasing attention, as they can precisely manipulate the fluid in a microscale channel or structure. Microfluidics-based biochemical sensing has been popularly used for various applications benefitting from the intrinsic advantages of low reagent consumption, rapid reaction rate, high throughput, easy integration, and facile automation. However, microfluidic device-based biochemical sensing is still limited by conventional signal readout that relies on sophisticated instruments and trained operators. Hence, the exploration of simplified signal readout is a critical issue in the development of microfluidic device-based biochemical sensing. In this review, equipment-free and low-cost signaling approaches for microfluidics are summarized, including colorimetric-readout, distance-readout, and smartphone-readout. Several other simplified signal readouts with potential to be integrated into microfluidics are described as well. Additionally, the prospects and challenges of simplified signal readout-based microfluidic devices are discussed.