Echovirus 18 (E18) is one of the most common enteroviruses, which cause aseptic meningitis, leukoencephalitis, and acute exanthema. No treatments against E18 are available and its structure is unknown. Here we present a cryo-EM study of E18 genome release and its inhibition by a capsid-binding compound. The structure of E18 virion was determined to the resolution of 3.2 Å. We show that binding of an inhibitor WIN51711 replaces a natural pocket factor within capsid protein VP1, but its binding does not cause any changes in the overall capsid structure relative to the native virus. However, the compound effectively decreases infectivity of the virus, probably by blocking of the genome release. Structure of so called “A” particle of E18 shows changes in its capsid that enable subsequent genome release. Similar to other enteroviruses the E18 A-particle contains pores along twofold symmetry axes.