The production of lignocellulytic enzymes by microwave-radiated Pleurotus sajor-caju was assayed. Wheat straw was employed as substrate to P. sajor-caju for production of laccase, manganese peroxidase (MnPase), filter-paperase (FPase), carboxmethyl cellulase (CMCase), and cellulase (as evaluated using microcrystalline cellulose). P. sajor-caju exposed to 10 s of microwave radiation (MR) showed maximum growth with colony radius of 7.17 ± 0.45 cm, while with increasing the exposure time up to 50 s the growth decreased up to 2.67 ± 0.22 cm. Moreover, it failed to grow at 80 s of exposure time. Cellulase, MnPase, FPase, CMCase, and laccase activities were induced to 37 ± .0.54, 49 ± 2.36, 189 ± 2.12, 0.37 ± 0.06, and 1.58 ± 0.03 U/mL compared to that at control 31 ± 0.25, 46 ± 1.25, 177 ± 1.65, 0.28 ± 0.03, and 1.37 ± 0.12 U/mL, respectively as a result of P. sajor-caju exposure to 10 s of MR. As the exposure time increased, these enzymes activity decreased. Different levels of moisture with surfactant (polysorbate 80) were applied to optimize the enzymes activities at 10 s of exposure time. The optimum activities 3.15 ± 0.23, 0.62 ± 0.06, 269 ± 5.36, 65 ± 1.63, and 48 ± 0.98 U/mL were recorded for cellulase, MnPase, FPase, CMCase, and laccase, respectively at 70% of moisture and 0.15 mL/L of polysorbate 80.