In this work, we demonstrated (1) that the combination effectively attenuated BPH development in rats through the quantitative analysis of histopathology and the prostate index, (2) that the combination treatment decreased the production of both dihydrotestosterone (DHT) and 5α-reductase, (3) that inflammatory responses can be greatly reduced via combination therapy in the BPH model of rats and (4) that AKT1, TNF, EGFR, STAT3 and PTGS2 are main targets which are associated with the anti-BPH activity of lycopene and curcumin. This evidence concerns the gene EGFR and benign prostatic hyperplasia.