The inclusion complex of diclofenac sodium (DCFNa) and beta-cyclodextrin (betaCD) was prepared and analyzed by using Raman and SERS spectroscopy. The interaction between DCFNa and betaCD molecules was evidenced by monitoring the change in the peak positions and the widths of some guest molecule bands relative to those observed in the spectra of the free compound and 1:1 DCFNa-betaCD physical mixture. Raman data have shown that the interaction between the guest and host molecules in the 1:1 DCFNa-betaCD complex is maintained both through the dichlorophenyl ring and the phenylacetate group. SER spectra revealed that depending on the pH value of the solution different isomeric forms of the 1:1 guest-host complex are preferentially adsorbed on the silver surface via the nonbonding electrons of the oxygen atom. The orientation of the adsorbed species with respect to the metal surface was also elucidated.