The resonant acoustic band gap materials have introduced an innovative generation of sensing technology. Based on the local resonant transmitted peaks, this study aims to comprehensively investigate the use of periodic and quasi-periodic one-dimension (1D) layered phononic crystals (PnCs) as a highly sensitive biosensor for the detection and monitoring of sodium iodide (NaI) solution. Meanwhile, a defect layer is introduced defect layer inside the phononic crystal designs to be filled with NaI solution. The proposed biosensor is developed based on the periodic PnCs structure and quasi-periodic PnCs structure. The numerical findings demonstrated that the quasi-periodic PnCs structure provided a wide phononic band gap and a large sensitivity compared to the periodic one. Moreover, many resonance peaks through the transmission spectra are introduced for the quasi-periodic design. The results also show that the resonant peak frequency changes effectively with varying NaI solution concentrations in the third sequence of the quasi-periodic PnCs structure. The sensor can differentiate between concentrations ranging from 0 to 35% with a 5% step, which is extremely satisfying for precise detection and can contribute to a variety of issues in medical applications. Additionally, the sensor provided excellent performance for all the concentrations of the NaI solution. For instance, the sensor has a sensitivity of 959 MHz, a quality factor of 6947, a very low damping factor of 7.19 × 10⁻⁵, and a figure of merit of 323.529.