A series of 2,4-dichloro-5-fluorophenyl chalcones were synthesized from 2,4-dichloro-5-fluoroacetophenone with various substituted benzaldehydes by crossed aldol condensation. The synthesized chalcones were characterized by their physical constants and spectral data. The UV absorption (λmax, nm), infrared spectral frequencies (ν, cm-1), and NMR chemical shifts (δ, ppm) of these chalcones were correlated with Hammett substituent constants, F and R parameter using single and multi-liner regression analysis. From the results of statistical analysis, the effects of substituent on the spectral group have been discussed. The antibacterial and antifungal activities of synthesized chalcones have been measured by Kirby-Bauerdisc-diffusion method.