Influence of loneliness on human survival has been established epidemiologically, but genomic researchremains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for highlonelyand low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtainedcorresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore,risk scores could be generated with the combination of gene expression level multiplied by correspondingregression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shortermean survival time than their low-risk score counterparts. Then we validated the loneliness-associated genesignature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191),significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3),lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06,p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Lonelinessassociatedgenes had good survival prediction for cancer patients, especially bone cancer patients. Our studyprovided the first indication that expression of loneliness-associated genes are related to survival time of cancerpatients.