Sleep-wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3 T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3 T cells (OR = 1.07, 95% CI = 1.01-1.13, = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85-0.98, = 0.014). Our results indicate that increased CD3 T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3 T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.