In the present work, we characterized PDI isoform contents in various cancer cell lines and provided evidence that PDIA1 and PDIA3 represent major isoforms of multiple cancer cells, and the non-selective inhibition of PDIA1 and PDIA3 displayed significant anti-proliferative effects irrespective of whether or not PDIA17 was present. The gene discussed is PDIA3; the disease is cancer.