Objective To investigate the impact of tumor-specific growth factor (TSGF) and Golgi glycoprotein-73(GP73) levels onthe prognosis of patients with primary hepatic cancer (PHC). Methods The clinical data of 78 patients with PHC (PHCgroup), 45 patients with liver cirrhosis (liver cirrhosis group) and 35 healthy volunteers (healthy group) were collected. Levels of TSGF and GP73 in the three groups were compared. Patients with PHC were followed up and the 3-year overall survival rate after treatment was recorded. Factors influencing the prognosis of patients with PHC, the correlation between TSGF and GP73 levels and the prognosis of patients with PHC were analyzed. Results Serum TSGF and GP73 levels in the three groups decreased in order (P<0.05). 58 out of the 78 patients with PHC survived in 3 years after surgery, with an overall survival rate of 74.36%. The proportions of high differentiation, clinical stage I, non-lymph node metastasis, wide surgical margins and single tumor in the survival group were significantly higher than those in the death group, while the grade of non-microvascular invasion, serum TSGF and GP73 levels were significantly lower than those in the death group (P<0.05). Binary Logistic regression analysis showed that lymph node metastasis, microvascular invasion, serum TSGF and GP73 levels were influence factors of the prognosis of patients with PHC (P<0.05). Correlation analysis showed that serum TSGF and GP73 levels in patients with PHC were significantly negatively correlated with the survival (P<0.05). Conclusion Serum TSGF and GP73 levels in patients with PHC are significantly negatively correlated with the prognosis. Closely monitoring serum TSGF and GP73 levels in patients with PHC before surgery may provide reference for early prognosis evaluation.