In this work, bioinformatics analysis, molecular modeling, and surface plasmon resonance experiments were employed to demonstrate that triptolide (TPL) and hesperidin (HSP) possess a common target (i.e., the epidermal growth factor receptor, EGFR) in bladder cancer (BCa) cells, and that both drugs exhibit a high affinity for the EGFR. This evidence concerns the gene EGFR and urinary bladder carcinoma.