Chalcogenides are the most promising candidates for nonlinear optical (NLO) applications in the middle infrared region due to their high nonlinear coefficients and wide IR transmission ranges. In particular, polar tetrahedral units are one type of typical functional motifs contribute large NLO coefficients. Based on this background, two quaternary selenides Na2Ga3In3Se10 (1) and Na2Ga3.76In2.24Se10 (2) were derived using NaIn3Se5 as parent. By partial congener substitution of In with Ga, the structure transforms from P32 for NaIn3Se5 to R32 for 1 and 2. Their 3D structures are constructed by InSe4 and GaSe4 tetrahedra, and Na+ ions occupy the octahedral cavities. Both of them exhibit wonderful hybrid NLO properties, witnessed by their large phase-matchable second harmonic generation responses of 1.5 (1) and 1.1 (2) × AgGaS2 (AGS), and enhanced laser-induced damage thresholds of 2.0 (1) and 2.8 (2) × AGS. The results of first-principle calculations show that their band gaps are mainly determined by the valence orbitals of Ga and Se, with a minor contribution from In. The simple design strategy adopted in this work can stimulate more research on various known materials, which will provide useful inspiration for further exploration of high-performance NLO materials. Besides, the successful discovery of 1 and 2 will stimulate more interest in the undeveloped A-MШ3-Q5 or A2-MШ6-Q10 (A = alkali metal; MШ = Ga, In; Q = S, Se, Te) family and their derivatives in the NLO field.