In this study, a series of 4,5-bis(substituted phenyl)-4
H
-1,2,4-triazol-3-amine compounds was designed, synthesised, and evaluated to determine their potential as anti-lung cancer agents. According to the results of screening of lung cancer cell lines A549, NCI-H460, and NCI-H23
in vitro
, most of the synthesised compounds have potent cytotoxic activities with IC
50
values ranging from 1.02 to 48.01 µM. Particularly, compound 4,5-bis(4-chlorophenyl)-4
H
-1,2,4-triazol-3-amine (
BCTA
) was the most potent anti-cancer agent, with IC
50
values of 1.09, 2.01, and 3.28 µM against A549, NCI-H460, and NCI-H23 cells, respectively, meaning many-fold stronger anti-lung cancer activity than that of the chemotherapeutic agent 5-fluorouracil. We also explored the effects of
BCTA
on apoptosis in lung cancer cells by flow cytometry and western blotting. Our results indicated that
BCTA
induced apoptosis by upregulating proteins BAX, caspase 3, and PARP. Thus, the potential application of compound
BCTA
as a drug should be further examined.