Objective To observe the effect of forkhead box Q1(FOXQ1) short hairpin RNA (shRNA) on sensitivity of oxaliplatin chemotherapy in hepatpcellular carcinoma cell line SMMC-7721. Methods ① Complementary shRNA oligonucleotides targeting the FOXQ1 gene and negative control-shRNA were designed and inserted into lentiviral vector. shRNA lentivirus vectors were transfected into SMMC-7721 cells and the lentivirus vector with the best silencing effect was screened. ② SMMC-7721 cells were divided into interference group (SMMC-7721 cells were transfected with FOXQ1-shRNA-1), negative control group (SMMC-7721 cells were transfected with negative control-shRNA), and blank control group (SMMC-7721 cells did not received any treatment), and the expressions of FOXQ1 mRNA and its protein in SMMC-7721 cells were detected at 72 hours after transfection. ③ SMMC-7721 cells were divided into interference group, negative control group, blank control group, interference+oxaliplatin group, negative control+oxaliplatin group, and blank control+oxaliplatin group, apoptosis rates and viability of SMMC-7721 cells were detected at 48 hours after transfection. Results ① The expressions of FOXQ1 mRNA and its protein in SMMC-7721 cells of the FOXQ1-shRNA-1 group were both lower than those of the FOXQ1-shRNA-2 group and FOXQ1-shRNA-3 group (P<0.05), so the FOXQ1-shRNA-1 was the best lentiviral vector. ② Compared with the negative control group and the blank control group, the expressions of FOXQ1 mRNA and its protein of the interference group were both lower (P<0.05), but there was no significant difference between the negative control group and the blank control group (P>0.05). ③ Whether added oxaliplatin or not, compared with the negative control group and the blank control group, the apoptosis rates of the interference group were higher (P<0.05), but the viability of the interference group was lower (P<0.05), and there was no significant difference between the negative control group and the blank control group under the same condition (P>0.05). The apoptosis rates of groups (including the interference group, the negative control group, and the blank control group) which added oxaliplatin were higher than those groups didn’t add oxaliplatin (P<0.05), but viability of groups (including the interference group, the negative control group, and the blank control group) which added oxaliplatin was lower than those groups didn’t add oxaliplatin (P<0.05). Conclusion Down-regulation of expression of FOXQ1 by shRNA in hepatocellular carcinoma cell line SMMC-7721 can effectively induce apoptosis and increase sensitivity of SMMC-7721 cells to oxaliplatin.