Abstract: Objective To investigate associations of single nucleotide polymorphism (SNP) of cell circle signaling pathway genes CDC25C,CDKN2A(p16),MCM4,MCM7,PARDC (DNA-PK),RAD21,RBL2 (p107),YWHAB (14-3-3),SMAD3,KAT2B,and CHEK1 with clinico-pathological characteristics of hepatocellular carcinoma (HCC) and to provide evidences for conducting HCC prognosis.Methods All newly diagnosed HCC patients (498) seeking medical service at Hepatobiliary Surgery of First Hospital Affiliated to Guangxi Medical University were recruited between July 2007 and March 2011.Medical records,relevant information,and peripheral blood samples of the patients were collected and the SNP of 14 cell circle signaling pathway genes of the patients were genotyped using the matrix-assisted laser desorption ionization-time of flight mass spectrometry method.Results After adjusting for age,gender,nationality,family history of HCC,hepatitis B surface antigen (HBsAg),smoking and alcohol drinking status,the results of unconditional logistic regression analysis indicated that the patients with YWHAB rs2425675 genotype AG/AA had a 2.097 times of risk for suffering from capsule invasion compared to the patients with genotype GG (odds ratioOR=2.097,95% confidence interval95%CI:1.034-4.256);the patients with RBL2 rs3929 genotype GC/CC had a significantly higher risk for suffering from capsule invasion risk compared to the patients with genotype GG (OR=2.234,95%CI=1.100-4.534),while the patients with CDC25C rs3734166 genotype GA/GG had a significantly lower risks of suffering from satellite tumor nodule (OR=0.460,95%CI=0.259-0.816) and tumor thrombi (OR=0.651,95%CI=0.439-0.965) compared to the patients with genotype AA;the patients with CHEK1 rs515255 genotype TC/TT showed significantly lower risks of suffering from satellite tumor nodule (OR=0.451,95%CI=0.252-0.80) and multiple tumor (OR=0.655,95%CI=0.442-0.971) compared to the patients with genotype CC.The results of stratified analysis indicated that SNP of YWHAB rs2425675 was significantly associated with incidences of capsule invasion and pseudocapsule among the patients without family HCC history,not smoking,not drinking alcohol (all P<0.05);SNP of CDC25C rs3734166 was significantly associated with incidences of satellite tumor nodule,tumor thrombi,cirrhosis,and vessel invasion among the patients without family HCC history,not smoking,not drinking alcohol,and HBsAg positive or negative (all P<0.05);SNP of CHEK1 rs515255 was significantly associated with incidences of capsule invasion,tumor thrombi and multiple tumor among the patients without family HCC history,not smoking,drinking alcohol or not drinking alcohol but HBsAg-positive (all P<0.05);SNP of RBL2 rs3929 was significantly associated with incidences of capsule and vessel invasion among the patients smoking or not smoking,drinking or not drinking alcohol,and HBsAg-negative (all P<0.05).Conclusion Gene polymorphism of CDC25C,CHEK1,YWHAB and RBL2 may be associated with clinico-pathological characteristics of HCC.