Hepatocellular carcinoma (HCC) has an extremely poor prognosis which is caused mainly by high frequency of metastatic recurrence. We previously reported that high interleukin (IL)-2 levels in peritumoral tissue were closely associated with a decreased incidence of intrahepatic tumor recurrence in patients with hepatitis B virus (HBV)-associated HCC, and the immune staining of IL-2 primarily was found in tumor-surrounding hepatocytes. However, whether hepatocytes can express IL-2 in vitro and underlying mechanism remain to be investigated. Here, we compared IL-2 expression levels in peritumoral tissue from HCC patients between HBV-positive group and HBV-negative group. We then overexpressed HBV x protein (HBx) in immortalized human liver cell line THLE-2, and mimic microenvironmental oxidative stress with hydrogen peroxide (H₂O₂) treatment in vitro. We demonstrated that hepatocytes can express IL-2 in vitro through MAP3K7/NF-κB pathway in the presence of both HBx stimulation and mild oxidative stress. Targeting microenvironmental oxidative stress offers a promise for prevention and therapy of HBV-associated HCC metastatic recurrence.