Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA).  In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated.  The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency.  Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC₅₀ of 2.84 μmol·L⁻¹ against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.