Abstract Controlling and patterning the surface charges of the sensing nanochannel in a resistive pulse sensing (RPS) device to enhance the signal detection are investigated in this paper. The electric currents and signal detection in the sensing nanochannels with positive surface charges, negative surface charges, and opposite surface charges at the two ends are systematically studied. It is found that the length of the surface-modified nanochannels has a significant effect on the sensitivity of the RPS detection. The pulse signal amplitude can be increased by 3 times in the surface-modified nanochannel when the channel length is 500 nm. The enhancement in the signal amplitude becomes less prominent in long nanochannels. Modified sensing nanochannels with a channel length of 5 μ m are fabricated by regulating surface charges with charged polyelectrolytes. Nanoparticles with a diameter of 5 nm are detected in the modified nanochannels. The experimental results are in good agreement with the numerical simulation results. It is also found that the surface charge pattern of the sensing nanochannel has a significant effect on the sensitivity of the RPS detection. The RPS signals can be enhanced by approximately 50 % when the sensing nanochannel has a section with positive surface charge and negative surface charge in the rest channel in a KCl solution with a bulk concentration of 100 mM.