The motion responses of cylinder Floating Production Storage and Offloading (FPSO) under different simulated ocean currents in the laboratory are investigated. The key characteristics of the motion responses are analyzed in frequency domain and time domain. The current is modeled by direct applying the equivalent current force and current generated in basin. The results show that: the change in the full loaded and ballast loading condition is of little effect on the motion of FPSO; directly applying the equivalent current force is of barely influence on the form of cumulative distribution of 6 Degree-of-Freedom (DOF) responses, but with slightly changes in the equilibrium position of 6 DOF responses; considering wave-current interaction, the surge amplitude increases significantly even if the reduced velocity is less than the lock-in region. Because the real environments can be harsher than the experimental one, the wave–current interaction should be taken into consideration when designing FPSO. With the coupling of current, the transverse motion tends to be distributed in a wider range with larger amplitude. The spectral peak frequency in Low-Frequency (LF) moves to lower frequency for sway and pitch responses under wave-current interaction. And the mean amplitude of LF and Wave-Frequency (WF) of 6 DOF responses are also significantly amplified.