Controlling the molecular arrangement by introducing halogen element substituents is a very effective crystal design method. Therefore, four chalcone derivatives, EFDAN, ECDAN, EBDAN, and EIDAN, were synthesized by introducing F, Cl, Br, and I, respectively. The tunable crystals containing Cl and Br elements with appropriate size have a better spatial arrangement, which is conducive to the increase of nonlinearity. Theoretical calculations indicate that electron transfer from the amino group and the adjacent benzene ring to the conjugated bridge is the main contributor to the crystal nonlinearity. Meanwhile, all four crystals have higher transparency, greater thermal stability, and lower dielectric constant. This work realizes the control of crystal structure through the rational replacement of halogen elements and provides a feasible idea for the design of other organic nonlinear materials.