An experimental demonstration of direct-detection single-sideband Nyquist-pulse-shaped 16-QAM subcarrier modulated (Nyquist-SCM) transmission implementing a receiver-based signal-signal beat interference (SSBI) cancellation technique is described. The performance improvement with SSBI mitigation, which compensates for the nonlinear distortion caused by square-law detection, was quantified by simulations and experiments for a 7 × 25 Gb/s WDM Nyquist-SCM signal with a net optical information spectral density (ISD) of 2.0 (b/s)/Hz. A reduction of 3.6 dB in the back-to-back required OSNR at the HD-FEC threshold was achieved. The resulting reductions in BER in single channel and WDM transmission over distances of up to 800 km of uncompensated standard single-mode fiber (SSMF) achieved are presented.