Hura crepitans (Euphorbiaceae) is a tree from South America that produces an irritant latex used as a fish poison. A bio-guided fractionation of an ethanolic extract of the latex led to the isolation and structural identification of three known daphnane-type diterpenes (1–3) including huratoxin (1), together with two new analogs (4, 5). Compound 1 was found to exhibit significant and selective cell growth inhibition against the colorectal cancer cell line Caco-2, with morphological modifications suggesting formations mimicking the intestinal crypt architecture. The underlying mechanism of 1 was further investigated, in comparison with 12-O-tetradecanoylphorbol-13-acetate (TPA), revealing two different mechanisms.