Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0μM and 8.0μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4μM IC50. Rest of the compounds (1, 3-9) showed 10.4-28.1μM IC50 on COX-2 and 17.0-35.6μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1-9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100μM for all compounds (1-9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.