Resonant cantilever mass sensors (RCS) can quantitatively detect the unknown analyte by measuring the frequency shift induced by attached the mass of analyte. With the characteristics of high sensitivity, long term stability and easy interfacing with digital signal processing, such sensors have been successfully applied in various application fields such as proteomics, genomics, gas sensing, food contamination, cancer detecting, chemical or fluidic detection. Recently, a great deal of attention has been paid on developing high sensitivity sensors that can be used outside of laboratory environments. According to the operating principle of the resonant sensor, the mass sensitivity is mainly depending on the ratio of the resonant frequency at mode number n to the corresponding effective mass of the resonant cantilever. Simultaneously increasing the resonance frequency and reducing the effective mass can effectively improve the mass detection sensitivity. As reported in many references, reducing geometry dimensions to increase the natural frequency by MEMS or NEMS technology is an effective way to improve sensitivity and spatial resolution of resonance mass sensors. Due to the limitation of the equipment for measuring the nano-sized cantilever deflection, the geometrical size reduction method encounters a bottleneck in improving the sensitivity. Different from the method of reducing the cantilever dimension, a new sensitivity improving method was proposed to inspire high-order mode by optimizing the stiffness and mass distribution of the cantilever. Through theoretically analyzing the relationship among structural parameters, vibration modes and the sensitivity, a novel piezoelectric resonant mass sensor working in the fourth order vibration mode is designed and fabricated. The experimental sensitivity of the proposed sensor is 1884100 Hz/g nearly 19.5 times greater than that of the custom rectangular cantilever sensor of 98500 Hz/g. The simulated sensitivity is nearly consistent with that of the experiment with the deviation of 1.28%. Meanwhile, the quality factor is 82.65, which is about 3.5 times as great as that of the rectangular uniform cantilever sensor with the same size, hence, validates the feasibility and effectiveness of the newly proposed sensitivity improving method.