The signal compensation method based on Wiener filtering has been demonstrated to have excellent compensation performance towards the signal distortion induced by the long-distance transmission in coaxial cable. However, factors affect the compensation performance of this method had not been investigated and analyzed, thus we carried out a systematic study on the effect of the parameters and the means of this modified method. The results show the main factors are the signal-to-noise ratio (SNR), the sampling frequency interval Δf in S₂₁ parameter measurement, and the power spectrum estimation method. When the SNR is less than 25 dB, the compensation performance continuously improves as the SNR increases. Once the SNR exceeds 25 dB, the relative error (δ) between the compensated signal and input signal nearly keeps unchanged. The compensation performance keeps unchanged when Δf is small, and it slowly deteriorates as Δf exceeds a certain value. It is proved that among the traditional power spectrum estimation methods, the Burg method can obtain the best compensation performance. This study can provide a beneficial reference for the application of the signal compensation method based on Wiener filtering.