Nuclear-related facilities can be detrimentally affected by ground vibrations due to the collapse of adjacent cooling towers in nuclear power plants. To reduce this hazard risk, a design-oriented acceleration response spectrum (ARS) was proposed to predict the dynamic responses of nuclear-related facilities subjected to ground vibrations. For this purpose, 20 computational cases were performed based on cooling tower-soil numerical models developed in previous studies. This resulted in about 2664 ground vibration records to build a basic database and five complementary databases with consideration of primary factors that influence ground vibrations. Afterwards, these databases were applied to generate the design-oriented ARS using a response spectrum analysis approach. The proposed design-oriented ARS covers a wide range of natural periods up to 6 s and consists of an ascending portion, a plateau, and two connected descending portions. Spectral parameters were formulated based on statistical analysis. The spectrum was verified by comparing the representative acceleration magnitudes obtained from the design-oriented ARS with those from computational cases using cooling tower-soil numerical models with reasonable consistency. Keywords: Ground vibration, Structural collapse, Response spectrum, Nuclear power plant