In this paper, a multi-pass retro-reflection-cavity-enhanced photoacoustic spectroscopy (PAS) based gas sensor is reported for the first time. The multi-pass retro-reflection-cavity consisted of two right-angle prisms and was designed to reflect the laser beam to pass through the photoacoustic (PA) cell four times, which improved the acetylene (C2H2)-PAS sensor signal level significantly. The optical power of a near-infrared distributed feedback (DFB) diode laser emitting a continuous wave (CW) was amplified to 1000 mW with an erbium-doped fiber amplifier. The background noise was reduced with wavelength modulation spectroscopy (WMS) and 2nd harmonic demodulation techniques. The linear optical power and concentration response of such a PAS sensor were investigated, and the experimental results showed excellent characteristics. When the integration the time of the sensor system was set to 1 s, the minimum detection limit (MDL) for C2H2 detection was 8.17 ppb, which corresponds to a normalized noise equivalent absorption coefficient (NNEA) of 1.84 × 10−8 cm−1W/√Hz. The long-term stability of such a multi-pass retro-reflection-cavity-enhanced PAS based C2H2 sensor was evaluated by an Allan deviation analysis. It was demonstrated that the multi-pass retro-reflection-cavity-enhanced PAS sensor had an excellent stability. An MDL of 600 ppt was achieved when the integration time was set to ~1000 s. It was verified that the method of multi-pass retro-reflection-cavity-enhanced PAS with an amplified laser source improved the sensor performance significantly. If an appropriate cavity design with increasing reflection times is used, the MDL of such a PAS-based sensor can be further improved.