RAMEC is a phase II, multi-center, randomized trial with a safety test. There will be a safety test to establish the safety and tolerability of Neo-MASCT treatment and assess the immune response to the treatment.The randomized trial will assess DFS and immune response.

The safety test will recruit 10 patients. Following registration they will receive 3 cycles of Neo-MASCT treatment. Patients will be seen at week 1, week 2 and week 4 of every cycle.

Following the safety test, 98 patients will be randomized to the trial across 3 recruiting centers. All patients on the treatment arm will complete up to 18 cycles of Neo-MASCT treatment. Patients on the control arm will be actively monitored after randomization. Blood samples for immune response test will be taken at baseline, cycle 1day 1 and then 3 monthly on day 1 of the subsequent cycles. The planned treatment duration will be until relapse of disease, unacceptable toxicity or withdrawal of consent. The end of the trial will be 24 months after the recruitment of the last patient.

Inclusion Criteria before resection/RFA:

1. Aged ≥ 18 years;
2. Primary HCC received RFA/Hepatectomy as the initial treatment; a solitary tumour 2.0-5.0m in diameter; or 2-3 tumours with the largest ≤5.0cm; all without vascular invasion, lymphatic metastasis or distant metastasis (see Appendix 1 for diagnosis criteria).
3. ECOG 0/1 (Appendix 3);
4. Child-Pugh score 5-7 (Appendix 4);
5. A life expectancy of 6 months or more；
6. Adequate haematological, liver and renal function Neutrophil count ≥1.5 x 109/L; platelet count> 60 x 109/L; Haemoglobin concentration≥9.0 g/dL; Serum albumin≥ 3.0 g/dL; A total bilirubin of less than 1.5 times upper limit of normal; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times upper limit of normal; Prothrombin time ≤3s above the control Serum creatinine concentration of 1.5 times the upper limit of the normal range or less; CCR ≥60ml/min
7. Written informed consent

Exclusion Criteria:

1. Pregnant women, lactating women or women planning to be pregnant in 2 years;
2. Intrahepatic metastasis, tumour thrombosis in main trunk or main branches of portal vein, tumour thrombosis in hepatic vein;
3. Systematic use of potent immunosuppressive agents within 6 months or long-term use of them such as corticosteroids, cyclosporine A, et al;
4. Concomitant HIV or HCV infection;
5. Concomitant immunodeficiency diseases or autoimmune diseases (eg. rheumatoid arthritis, Buerger's disease, multiple sclerosis and type I diabetes);
6. Concomitant malignancy or previous malignancy within 5 years before enrolment, excluding skin cancer, local prostate cancer or cervical carcinoma in situ;
7. Organ transplant recipients;
8. Patients with active auto-immune disorder, e.g. autoimmune hepatitis, systemic lupus erythematous etc.;
9. Severe dysfunction of the heart, kidney, or other organs;
10. Severe psychological dysfunction;
11. Sensitive to cytokines, any reagent or associated component in MASCT;
12. Ever participated in any clinical trial of other drugs within 3 months before enrolment;
13. Other patients that investigators think unsuitable to be enrolled.

Inclusion Criteria before immunotherapy:

1. Imaging (enhanced CT or MRI) confirmed completely tumor necrosis or tumor removed 4 weeks after RFA/Hepatectomy；
2. Obtaining adequate samples of the matched tumor and adjacent nontumor normal liver tissues;
3. Sensitive mutations can be detected by gene sequencing in tumour tissue;
4. Prediction of neoantigen peptides ≥10;
5. Synthesized neo antigen peptides ≥5.