The optimized optical phase conjugation (OPC) configuration is proposed for the 40-Gb/s CO-OFDM system. The proposed configuration for nonlinear cancellation is systematically depicted in transmission links with lumped amplification. Numerical simulations are performed to demonstrate effectiveness. Simulation results show that mid-span spectral inversion (MSSI) can partially compensate for nonlinear distortions. Moreover, its optimized configuration can further improve system performances and increase nonlinear compensation effectiveness. Compared with MSSI, the maximal Q factor, nonlinear threshold, and transmission distance of optimized OPC configuration increase by over 1.6 dB, 2 dB, and 2 times, respectively.