Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) has garnered significant attention as a subfield of SERS detection due to its capacity to regulate the band gap between molecules and substrates through pressure modulation. Currently, SERS detection primarily focuses on single molecules at atmospheric pressure with limited investigations conducted under high pressure conditions. Herein, we employed rose-shaped MoS 2 nanoflowers as the SERS substrate and realized selective PI-SERS enhancement of R6G molecules in the binary (MV+R6G) and ternary (MV+R6G+RhB) systems. The MoS 2 demonstrated an exceptionally low SERS detection limit of 5 × 10 −6 M in binary and ternary systems with equimolar amounts of molecules. Highpressure experimental results indicate that MoS 2 displays selective enhancement for R6G molecules, as evidenced by the comparison of the PI-SERS peak intensity ratio between MoS 2 and the probe molecules. The proposed enhancement mechanism in binary and ternary SERS systems under high pressure involves pressureinduced changes in both the band structures of the MoS 2 substrate and molecules, thereby influencing their charge transfer dynamics. Consequently, this approach holds great promise for practical applications in complex SERS systems operating under extreme conditions.