Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and a leading cause of tumor related death. Hepatectomy is considered to be the main radical treatment for HCC. However, the high recurrence rate remains a major challenge. Adjuvant therapy to effectively reduce recurrence is particularly important for patients (pts) with high recurrence factors. Transarterial chemoembolization (TACE) as adjuvant therapy for pts with high recurrence risk factors after hepatectomy is recommended in several guidelines, but the effect is still unsatisfactory. Here, we updated the results of ALTER-H004 which aimed to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Methods: Pts with histologically confirmed HCC and undertook hepatectomy within 1-2 months will be recruited in this study. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5 cm and < 10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II). Eligible pts received conventional TACE treatment with pirarubicin and platinum within 1-2 months after hepatectomy. On the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week of) was given until disease recurrence or unacceptable toxicity. The calculated sample size was 48. The primary endpoint was disease free survival (DFS). Secondary endpoints were 1-year DFS rate, time to recurrence and safety. Results: As of September 14, 2021, 24 pts were enrolled and 23 pts received at least once tumor assessment. According to RECIST 1.1, 17 of 24 did not progress were still on treatment and 5 relapsed. One withdrew the consent and 1 discontinued because of intolerable adverse events. The longest duration of treatment is 15.24 months. The DFS were not mature and the 6-month DFS rates were 75.11% (95% CI: 46.28̃89.91). 12 of 24 pts (50.0%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 pts (16.7%) included hypertension (29.2%), hyperbilirubinemia and hematologic toxicities. No grade 4 or 5 TRAEs occurred. Conclusions: Preliminary results suggested that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and manageable adverse events, which should be validated in more pts consecutively. Clinical trial information: NCT04213118.