In the work, laboratory experiments were designed to simulate the collisional plasma environment of the ionosphere. Neutral gas was injected to increase the ion-neutral collisions, and the ambient plasma subsequently transforms from the magnetospheric-like collisionless plasma to the ionospheric-like collisional one. In the collisionless plasma, the classical electrostatic Kelvin-Helmholtz instability (KHI) was generated using an interpenetrating plasma method. However, the collisionless KHI was dissipated in the collisional plasma and subsequently a new wave mode was excited. The mode was identified as the collisional KHI by comparing the experimental results with the theoretical wave dispersion relation. The result indicates that the KHI can be excited in the ionospheric-like collisional plasma, which could be applied to understand the generation mechanism of the ionospheric irregularities by the bottomside sheared flow.Plain Language Summary Ionospheric irregularities, in the form of density spikes and cavities, are universal in the ionosphere from low to high latitudes. The ionospheric irregularities have a significant impact on satellite radio communications. The Kelvin-Helmholtz instability (KHI) was considered to play a significant role in the generation of the ionospheric irregularities. However, a key issue is that the generation of KHI in a collisional plasma has not been experimentally verified. In the work, laboratory experiments were conducted to simulate the collisional environment of the ionosphere. The result suggests that the shear-driven KHIs can be generated in an ionospheric-like collisional plasma. Through our experimental work, the theoretical mechanism can be more confidently applied to explain the excitation of ionospheric irregularities.