The signature events caused by host-guest interactions in the nanopore system can be used as a novel and char-acteristic signal in quantitative detection and analysis of various molecules. However, the effect of several elec-trochemical factors on the host-guest interactions in nanopore still remains unknown. Here, we systematically studied host-guest interactions, especially oscillation of DNA-azide adamantane@cucurbit[6] inα-Hemolysin nanopore under varying pH, concentration of electrolytes and counterions (Li+, Na+, K+). Our results indicate correlations between the change of pH and the duration of the oscillation signal. In addition, the asymmetric elec-trolyte concentration and the charge of the counterions affects the frequency of signature events in oscillation signals, and even the integrity of the protein nanopore. This study provides insight into the design of a future bio-sensing platform based on signature oscillation signals of the host-guest interaction within a nanopore.