The substrate‐controlled regioselective conjugate addition (1,8‐ and 1,4‐addition) of tropones with difluoroenoxysilanes is reported, which offered an approach for the selective synthesis of multifunctional seven‐membered 3,5‐cycloheptadien‐1‐ones and 1,3‐cycloheptadien‐1‐ones featuring a gem‐difluoroketone moiety. Moreover, these fluorinated cyclo‐heptadienones exhibit effective anti‐proliferative activities (IC50 < 1 μM) for human colon carcinoma HCT116 cells in vitro, thus providing potential lead compounds for developing new anticancer agents.