Aims: This study investigated the serum levels of myostatin, follistatin and IL-6 in the patients with hepatocellular carcinoma (HCC), and their association with sarcopenia and survival. Methods: Using prospectively collected pretreatment serum samples obtained from 238 HCC patients from 2012 to 2015, serum levels of myostatin, follistatin and IL-6 were determined using commercialized ELISA. The cross-sectional area of the psoas muscles at the third lumbar level of CT normalized for the patient’s height was presented a psoas muscle index (PMI). Sex-specific cut-offs of PMI to define the sarcopenica were ascertained by the maximal chi-square method. Results: The subjects showed a median age of 59 years, 81% of male, and hepatitis B virus infection in 70%. The median myostatin levels for males and females were 3,979.3 pg/mL (819.33-21,652.1 pg/mL) and 2,976.3 pg/mL (901.5-15,652.9 pg/mL), respectively, with the levels of follistatin [2,118.5 pg/ mL (573.7-16,923.6 pg/mL, male); 2,174.6 pg/mL (675.1- 8,337.3 pg/mL, female)] and IL-6 [2.5 pg/mL (0.11-106.79 pg/ mL, male); 2.7 pg/mL (0.01-122.97 pg/mL, female)]. PMI was 4.48 ± 1.25 (males) and 2.25 ± 0.82 ㎠/㎡ (females), showing sarcopenic prevalence of 56.7%. The sarcopenic group showed a significantly higher follistatin level, larger tumor size, more advanced BCLC stage and higher overall mortality than non-sarcopenic group. On multivariate analysis, follistatin level (≥2100 pg/mL) was an independent factor for poor survival [hazard ratio, 2.197; 95% confidence interval (CI), 1.123-4.296; P=0.021] along with a low PMI, high alpha-fetoprotein level, MELD score and TNM stage. However, serum follistatin level was not correlated with PMI, while myostatin level showed a positive correlation with PMI (R_s = 0.271, P<0.001). Conclusions: Serum follistatin level, rather than myostatin or IL- 6, was an independent factor for poor survival in HCC patients. Further study on the role of follistatin in prognosis of HCC is warranted.