The development of new infrared (IR) nonlinear optical (NLO) materials with strong second-harmonic generation (SHG) responses and high laser-induced damage thresholds (LIDTs) is urgent but challenging. Herein, the defective diamond-like chalcogenide Hg 3 P 2 S 8 (HPS) was rationally designed and fabricated by a flexible and rigid tetrahedral motif combined strategy. HPS exhibits a phase-matching SHG response of ∼3.6 × AGS (the largest one in the reported ternary sulfides), high LIDT (∼3 × AGS), wide IR transparent region (0.43−16.3 μm), moderate birefringence (0.043 at 1064 nm), and good physicochemical stability and crystal growth habits. Theoretical analyses confirm that the large SHG effect originates from the synergistic effects between distorted HgS 4 , PS 4 , and vacancy-induced nonbonding electrons. The results indicate that HPS is a promising NLO candidate for high-power, high-efficiency laser output in the mid-IR region, which provides an insight into the exploration of new IR NLO materials.