Ester derivatives of p-hydroxycinnamic compounds have high anticancer activity. However, the ester compounds usually easier to be decomposed than their amide derivates, so the ester compounds have a low potential to be applied as anticancer. In this research, the amide derivatives of caffeic and p-coumaric acids have been synthesized using o-tolylamine to give trans-N-(o-tolyl)caffeamide (5a) and trans-N-(o-tolyl)-p-coumaramide (5b), respectively. The products were characterized by FT-IR, 13C-NMR, and 1H-NMR methods. In the FT-IR spectrum, compound 5a showed absorption bands of N-H bond at 3236.55 cm−1 and 1533.41 cm−1 as stretching and bending vibrations, respectively; and compound 5b had absorption bands at 3267.41 cm−1 and 1527.82 cm−1. In the 13C-NMR spectrum, compound 5a gave 15 of peaks that representing 16 of carbons, and compound 5b gave 14 of peaks that were also representing 16 of carbons. In the 1H-NMR spectrum, the peak of N-H of compound 5a and compound 5b appeared at 8.57 ppm and 8.87 ppm, respectively. Activity assay results of both compounds against P388 leukemia murine cells indicated that both compounds have a high potential as anticancer, especially compound 5a. The compound 5a was more active than the analogous compounds which the previous synthezised.