This paper investigates the influence of liquefaction of the weak interlayer on the vibration characteristics of the deep overburden and the seismic response of the high earth-rock dam. Initially，the deep overburden site with liquefiable interlayer is simplified into a three-particle system and the calculation formula of predominant period of site after liquefaction of soft interlayer is derived. Furthermore，the effects of the characteristic parameters of the liquefiable interlayer on the site predominant period and the response spectrum of the site are analyzed. Then，the effect of liquefaction of soft interlayer on acceleration amplification factor of the earth-rock dam on deep overburden is studied by shear wedge method. The results show that the liquification of the interlayer increases the site predominant period，and the degree of this increase is mainly related to the degree of softening of the liquefiable layer，the ratio of the overburden layer thickness to the thickness of the liquefiable layer λ1 and the ratio of the liquefiable layer thickness to the thickness of the substratum layer λ2. Liquefaction adds at least one class to the site category. The surface acceleration spectrum after liquefaction presents the phenomenon that the short-period of the acceleration spectrum decreases while the long-period increases，the division line between increasing and decreasing is generally 0.6-0.9 s，and the platform section of the response spectrum is widened. Liquefaction makes acceleration amplification factor of the high earth-rock dam on overburden obviously increase，and the magnification decreases with the increase of degree of softening of the liquefiable layer. When the interlayer is thick and heavily liquefied，the seismic response is weaker than that before liquefaction.