In cancer the process of anoikis is intimately associated with the emergence and progression. N6-methyladenosine modification and m6A modification play an important role in regulating long non-coding RNAs. The liver hepatocellular carcinoma patients’ data within clinical and prognostic data were obtained via The Cancer Genome Atlas database. The univariate, multivariate Cox and Least Absolute Selection Operator (LASSO) regression were performed to gain anoikis and m6A related lncRNAs. The Kaplan-Meier method employed to assess the overall survival rate for groups of the high-and low-risk.

A signature comprising six anoikis and m6A related lncRNAs was constructed: AL117336.3, LINC01138, Z83851.1, NRAV, CASC19 and AC009283.1. The clinicopathological variables, the anoikis and m6A-related lncRNAs signature demonstrated superior diagnostic efficacy, with an area under the receiver operating characteristic curve of 0.810. The high-risk group’ the overall survival was shown inferior to that of in group of low risk while patients were classified by distinct clinicopathological variables. The ssGSEA and CIBERSORT immune analysis demonstrated that the predictive signature was significantly associated with liver cancer patients’ immune status. The chemotherapy drugs ATRA, AUY922, bexarotene, gemcitabine, mitomycin-C, and PHA found be greater sensitivity in treating high-risk patients. qRT-PCR showed that Z83851.1, NRAV and CASC19 lncRNAs were associated with poor prognosis and were high risk factors. AC009283.1 lncRNA may have anti-cancer properties.