BACKGROUND: Postoperative recurrence is currently the main factor affecting the long-term survival of hepatocellular carcinoma (HCC) patients. The folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen with transarterial chemoembolization (TACE) is a commonly used postoperative chemotherapy strategy, but its effect is still limited. The aim of this study was to analyze the effects of recombinant human adenovirus type 5 (rhAd5) combined with TACE on postoperative metastasis and recurrence of HCC. METHODS: Patients with HCC undergoing surgical treatment were collected and divided into the rhAd5 group and control group according to whether rhAd5 was performed. The rhAd5 group was combined with rhAd5 treatment based on TACE. The recurrence and metastasis rates of the two participant groups were compared. The changes of liver function, kidney function, blood routine, and adverse reactions during treatment were analyzed. RESULTS: The basic data of the two groups were not significantly different (P>0.05). The recurrence and metastasis rates of rhAd5 group participants were significantly lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the rhAd5 group and control group (P>0.05). There were no significant differences in the incidences of adverse reactions between the rhAd5 group and control group (P>0.05). CONCLUSIONS: The combination of FOLFOX and rhAd5 after surgery can significantly inhibit the occurrence of metastasis and recurrence of HCC patients, improve progression free survival, and has certain safety.