A novel mixed-signal adaptable silicon-based coherent photoacoustic (PA) sensing system-on-chip (SoC) is proposed to sense versatile target PA signals accurately in noisy scenarios with interferences in a compact chip-level, attaining precise in vivo sensing for physiological signs monitoring and enhanced bio-imaging. Through using the configurable PA SoC supported by on-chip Gilbert cell-based multiplier, the digital processing module, and DACs, templates in quadrature to each other designated as in-phase (I) and quadrature (Q) are generated in each channel by digital chip module. The templates are configurable to own a highly similar profile to the PA signal induced by the object tissue, attaining detection and reconstruction of target signals by coherent operation. The correlation is implemented efficiently and adaptive tracking and accurate reconstruction on the object signals are implemented efficiently at the chip level. By using the mixed-signal PA SoC designed in the TSMC 65-nm CMOS process, precise in vivo sensing is realized at the edge. Further, as PA detection leverages optical and ultrasound sensing, in vivo imaging on in-depth vessels or other tissues can be assured.