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Long noncoding RNAs (lncRNAs) are anticipated to be significant players in the pathogenesis of HCC in a multitude of ways, including tumor progression, proliferation, invasion, metastasis, and recurrence. To limit the progression of hepatocarcinogenesis, we employ a new treatment regimen that delivers lncRNA SRHC via polymer nanoparticles. A total of 100 mice were divided into five different groups. The initial group served as a control and received saline injections. On the other hand, the pathological-control group received weekly N-Nitrosodiethylamine (DEN) injections for 16 weeks. The remaining three groups received injections of polymer nanoparticles (NPs), long noncoding RNA SRHC alone, or conjugated NPs, respectively, once a week for four weeks, starting in the 12th week after DEN injection. After 16 weeks, the animals were euthanized, and liver specimens and blood samples were collected for biochemical, molecular, and pathological evaluations. Using nanoconjugates containing the lncRNA SRHC significantly improved tumor-associated biomarkers and histopathology compared with the pathological-control group. Furthermore, the expression of SENP1 and PCNA was downregulated. 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