S-1 is a new chemotherapy drug. Some phase II trials showed S-1 is effective in Hepatocellular Carcinoma (HCC). S-1 combined with calcium folinate (SL) showed very good efficiency and safety in colorectal cancer (CRC). The short duration (two weekly regimen) is better than common course 4 week regimen in tolerance. So the investigators want to examine the efficiency and safety of SL one week on and one week off regimen in HCC.

S-1 is a new chemotherapy drug. Some phase II trials showed S-1 is effective in HCC. S-1 combined with calcium folinate (SL) showed very good efficiency and safety in CRC. The short duration (two weekly regimen) is better than common course 4 week regimen in tolerance. So the investigators want to examine the efficiency and safety of SL one week on and one week off regimen in HCC.

SL one week on and one week off regimen will be give to advanced HCC patients. The primary endpoint is durable complete response (DCR).

Inclusion Criteria:

• Male or female, 70 years > Age > 18 years
• Patient with unresectable primary hepatocellular carcinoma
• Child-Pugh Class A or B, without ascites
• ECOG score 0
• At least one tumor nodule can be evaluated by CT or MRI
• Can take medicine orally
• Expected survival time not less than 12 weeks
• Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to enrolling in this portion of the study During the trial and 4 week after the trial, must take contraception
• Patients must be:
• Hemoglobin > 9.0g/dl
• ANC > 1.5×109/L
• Platelet ≥ 60×109/L
• Total bilirubin < 3mg/dl
• ALT or AST < 5 X ULN
• ALP < 4 X ULN
• PT-INR < 2.3
• Patients who is taking Warfarin , should be tested every week till getting stable INR
• Serum creatinine < 1.5 X ULN
• Serum amylase and lipase < 2 X ULN

Exclusion Criteria:

• Known or suspected allergy to any agent given in association with this trial
• Local treatment within 4 weeks prior to start of study drug
• History of any heart disease
• History of HIV infection except for HBV and HCV
• Active clinically serious infections (> 2 NCI-CTC Version 3.0)
• Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry.
• Embolization or infarction such as transient ischemic disease, deep vein thrombosis, pulmonary embolization within 6 months prior to study entry
• Previous malignancy (except for cervical carcinoma in situ, adequate treated basal cell carcinoma, or superficial bladder tumors [Ta, Tis and T1], early gastric cancer, or other malignancies curatively treated > 3 years prior to entry
• Extrahepatic tumor spread which affects patient's prognosis, such as bony metastasis or brain metastasis
• Hydrothorax， ascites and hydropericardium need to drain
• Serious diarrhea
• Combined with serious pulmonary diseases, such as interstitial pneumonia, pulmonary fibrosis and serious pulmonary emphysema
• Serious complication,such as intestinal obstruction,renal insufficiency, hepatic insufficiency and cerebrovascular disorders
• Pregnant or breast-feeding
• Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment.
• Gastrointestinal disease that may affect to the absorption of drug or pharmacokinetics.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in this study
• Patients unable to swallow oral medications.