The magnitude and content of an earthquake is usually hard to be predicted precisely. To make seismic isolation systems more adaptive to earthquake motions that may have diverse characteristics, a semi-active isolation system called the "Piezoelectric Sliding Isolation System (PSIS)" is introduced in this study for the seismic protection of precision equipment. The PSIS system is composed of a sliding isolation platform and a piezoelectric friction damper (PFD). Depending on the feedback signal of the PSIS response, the friction force of the PFD can be regulated on-line by an embedded piezoelectric actuator. As a result, the seismic response of the PSIS can be effectively controlled and mitigated. The feasibility of the PSIS is verified dynamically via a shaking table test in this study, and the comparison between the experimental and theoretical results has shown the good consistency. The experimental results also demonstrate that, the PSIS is able to substantially suppress both the displacement and acceleration responses in an earthquake with either near-fault or far-field characteristics. The study also shows that, even though the semi-active PSIS system can only provide a passive control force, it is able to achieve the same level of control performance as an actively controlled isolation system, which shares the same optimal feedback gain as that of the PSIS.