The traditional operation mode of high-field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) uses a one-way radio frequency (RF) voltage input as the dispersion voltage. This requires a high voltage input and limits power consumption reduction and miniaturization of instruments. With higher dispersion voltages or larger compensation voltages, there also exist problems such as low signal intensity or the fact that the dispersion voltage is no longer much larger than the compensation voltage. In this paper, a differential-RF-driven operation mode of FAIMS is proposed. The two-way RF is used to generate the dispersion field, and a phase difference is added between the two RFs to generate a single step waveform field. Theoretical analysis, and experimental results from an ethanol sample, showed that the peak positions of the ion spectra changed linearly (R2 = 0.9992) with the phase difference of the two RFs in the differential-RF-driven mode and that the peak intensity of the ion spectrum could be enhanced by more than eight times for ethanol ions. In this way, it is possible to convert the ion spectrum peaks outside the separation or compensation voltage range into a detectable range, by changing the phase difference. To produce the same separation electric field, the high-voltage direct current input voltage can be maximally reduced to half of that in the traditional operation mode. Without changing the drift region size or drift condition, the differential-RF-driven operation mode can reduce power consumption, increase signal-to-noise ratio, extend the application range of the dispersion voltage and compensation voltage, and improve FAIMS detection performance.