To design nonlinear optical (NLO) materials, we focused on combinations of d10 metal cation (Cd2+)-based chloride and morpholine molecules to form organic-inorganic hybrids. The O of morpholine containing lone-pair electrons can be integrated with Cd2+ by a ligand-to-metal charge transfer (LMCT) strategy to build acentric structures benefiting from the second-order Jahn-Teller effect. Introduction of the high-electronegativity chlorine can make polyhedrons of acentric crystals more distorted and conducive to a strong second harmonic generation (SHG) response. Therefore, (Morpholinium)2Cd2Cl6 crystals were constructed and synthesized by a solvent evaporation method. (Morpholinium)2Cd2Cl6 belongs to the orthorhombic P212121 space group and shows a one-dimensional (1D) structure with distorted [CdCl6] and [CdCl4O2] octahedrons. The short cutoff edge of (Morpholinium)2Cd2Cl6 was determined to be about 230 nm. The SHG response of (Morpholinium)2Cd2Cl6 exhibited an intensity of approximately 0.73 × KDP as estimated by the powder second harmonic generation technique. Furthermore, related theoretical calculations were performed to study the relationship of the band structure, refractive anisotropy, electronic state, and nonlinear optical response. Besides, (Morpholinium)2Cd2Cl6 showed relatively good thermal stability. This work can serve as a guide for the design and synthesis of new large NLO hybrid crystals with d10 transition metals.