A series of novel unsymmetrically N,N′-substituted ureas were synthesized from dehydroabietic acid and their structures were characterized by IR, ¹H-NMR, ¹³C-NMR spectroscopy and single crystal X-ray diffraction. Three six-membered rings of urea 4c exhibited plane, half-chair and chair configurations, respectively. Their cytotoxicity activities against SMMC7721 liver cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The results showed that the title compounds exhibited highly effective cytotoxicity activities against SMMC7721 cells. Their IC₅₀ values are between 8.8 and 14.2 μmol/l. The change of N′ substituted groups resulted little difference to the cytotoxicity activities of ureas, which indicated that the cytotoxicity of this kind of ureas depend strongly on the tricyclic hydrophenanthrene structure.