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Development of new antiviral nucleic acid-based drugs and the search for their efficient delivery into cells are an urgent task. We prepared the TiO2·PL-DNA and TiO2·PL±DNA nanocomposites bearing DNA fragments immobilized on TiO2 nanoparticles through polylysine linker (PL) with either covalent or ionic bond between PL and DNA, respectively. The proposed nanocomposites can penetrate into cells without transfection agents. The DNA fragments in both types of the nanocomposites were shown to retain their ability to form complementary complexes. The nanocomposites TiO2·PL-dsDNA and TiO2·PL±dsDNA bearing the double-stranded DNA were also synthesized. The proposed nanocomposites were demonstrated to be efficient antiviral agents against influenza A virus (IAV) in the MDCK cell culture. The TiO2·PL-DNA and TiO 2·PL±DNA nanocomposites bearing the DNA fragments targeted to the 3’-noncoding region of IAV segment 5 inhibited virus replication by four and three orders of magnitude, respectively. Thus, the TiO2 ·PL-DNA nanocomposites appeared to be more efficient than the TiO2·PL±DNA nanocomposites. The antiviral activity of the nanocomposites can be improved by either increasing their capacity for the DNA fragment or using dsDNA. Control samples, i.e., nanoparticles without DNA fragments and vice versa, unbound DNA fragments in the presence of nanoparticles, and nanocomposites bearing DNA fragments with random sequences showed a negligible effect. The presented nanocomposites can be applied in the thriving technology of drug delivery to achieve high therapeutic and biological efficacy. [ABSTRACT FROM PUBLISHER]