The major findings of this study are that 1) thymoquinone (TQ) was identified as an HIF-1α inhibitor using a 502 natural compound library, 2) TQ suppressed hypoxia-induced HIF-1α by suppressing HSP90-mediated stabilization and target genes’ expression, 3) TQ alters hypoxic anaerobic glycolysis and causes metabolic stress, and 4) TQ selectively killed hypoxic renal cancer cells. This evidence concerns the gene HIF1A and renal carcinoma.