The quasi-isentropic compressibility of a strongly nonideal helium plasma in the pressure range 250–600 GPa is experimentally studied in devices with cylindrical geometry. The temperature at the front of a cylindrical shock wave in helium ( T ≈ 10 000 K) and the flight speed of the inner cascade ( W ≈ 3.5 km/s), in the cavity of which the maximum compressed plasma density is achieved, are measured. Data on the compression of a nonideal helium plasma to a density ρ ≈ 3 g/cm 3 at an approximately constant final temperature of 21000 K are obtained. The trajectories of the metallic shells compressing the plasma are detected using high-power pulsed X-ray sources with a boundary electron energy of up to 60 MeV. The helium plasma density is determined using the radii of the shells measured at the time of their “stop.” The compressed plasma pressure is obtained using gasdynamic calculations. Comparative theoretical calculations of the quasi-isentropic compression parameters have been carried out using the following two theoretical models: the traditional chemical plasma model (SAHA code) and an ab initio quantum molecular dynamics (QMD) approach. No anomaly of the experimental data in the pressure range of the plasma phase transition theoretically assumed in helium is detected.