Objective To compare the application effects of three psychometric instruments including SF-36, FLIC and QOL-LC in measuring the quality of life of patients with liver cancer. Methods A total of 105 in-patients with liver cancer selected from 2010 to 2011 were included. The quality of life was measured by FLIC, SF-36 and QOL-LC, respectively, and the reliability, validity and responsiveness were calculated and analyzed. Results The reliability and validity of QOL-LC were better than those of SF-36 and FLIC. Both QOL-LC and FLIC showed significant differences in responsiveness based on the changes of physical function and overall quality of life (QOL-LC: t=5.08, P=0.000, t=3.16, P=0.002; FLIC: t=4.02, P=0.000, t=2.21, P=0.030). Except for general health and mental health, the other domains of SF-36 showed significant differences in changes after treatment (physical function: t=5.94, P=0.000; physical role: t=3.07, P=0.003; body pain: t=3.21, P=0.002; vitality: t=3.22, P=0.002; social role: t=2.60, P=0.012; emotional role: t=3.28, P=0.002). Conclusion QOL-LC is a specific scale for liver cancer, and it should be used preferentially. SF-36 and FLIC can measure the general state of quality of life and can be used in patients with liver cancer when specific scale is not available.