Through the investigation of inhibitory effect on growth of HCC cells and phosphorylation of STAT3, we found that alminoprofen, never being studied in cancer treatment, had an effective anti‐tumor role on HCC cells through binding on C21orf58 and destroying the formation of C21orf58/JAK2/STAT3 complex, resulting in diminishment of STAT3 activity. This evidence concerns the gene C21orf58 and hepatocellular carcinoma.