In this study, we focused on the effect of KV9.3 on proliferation in HCT15 and A549 cells, demonstrating that (i) KV9.3 transcripts are expressed in HCT15 and A549 cells; (ii) KV9.3 knockdown decreases the viability of HCT15 and A549 cells by inducing cell cycle arrest in G0/G1 phase with no change in the proportion of apoptotic cells; (iii) stable KV9.3 knockdown HCT15 and A549 cells show decreased tumor growth in mouse xenograft; and (iv) the transcription factor Sp1 potentially regulates the expression of KV9.3. The gene discussed is SP1; the disease is neoplasm.