Cancer prevention is now most urgently required for public health, particularly targeting the promotion stage of carcinogenesis as it can be applied post-exposure to unavoidable tumor-initiating agents. Earlier studies demonstrated extracts from edible plants and crude drugs inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced inflammatory ear edema, and alkane-6,8-diols isolated from Carthamus tinctorius (safflower) inhibited TPA-induced ear edema and tumor promotion in mouse skin. This study prepared homologs 4a-c of the alkane-6,8-diol series. In mouse assays, C27- and C29-alkane-6,8-diols (4b,c) inhibited TPA-induced inflammatory ear edema with ID50 values of 0.5 and 0.4 mg/ear, respectively, comparable to indomethacin, more effective than quercetin (a known tumor promotion inhibitor) but less than hydrocortisone. C29-alkane-6,8-diol (4c) inhibited tumor promotion by TPA following 7,12-dimethylbenz[a]anthracene (DMBA) initiation: at week 20, the percentage of tumor-bearing mice decreased from 93% to 20%, and the average number of tumors per mouse from 11.1 to 0.9. Since safflower is nontoxic and used in foods, these alkane-6,8-diols are promising chemopreventive agents for cancer.