In this study, four hybrid organic-inorganic compounds (8-H2Q)2PdCl4 (1), (H2ClQ)2PdCl4 (2), (H2NQ)2PdCl4 (3) and (H2MeQ)2PdCl4·2H2O (4) (where 8-H2Q = 8-hydroxyquinolinium, H2ClQ = 5-chloro-8-hydroxyquinolinium, H2NQ = 5-nitro-8-hydroxyquinolinium and H2MeQ = 2-methyl-8-hydroxyquinolinium) were synthesized through organic cation modulation. Single-crystal X-ray structure analysis of compounds 1 and 3 indicates that their structures are planar and consist of PdCl42− anions and 8-H2Q or H2NQ cations, respectively. Both ionic components are held together through ionic interactions and hydrogen bonds forming infinite chains linked through π-π interactions to form 2D structures. Furthermore, NMR spectroscopy, UV–Vis spectroscopy, elemental analysis, and FT-IR spectroscopy were used to explore the synthesized compounds. The DNA interaction, antimicrobial activity, antiproliferative activity, and radical scavenging effect of the compounds were evaluated. The hybrid compounds and their free ligands can interact with the calf thymus DNA via an intercalation mode involving the insertion of the aromatic chromophore between the base pairs of DNA; compound 1 has the highest binding affinity. Moreover, they have high antimicrobial efficacy against the tested 14 strains of microorganisms with minimum inhibitory concentration values ranging from <1.95 to 250 μg/mL. The antiproliferative activity of the compounds was investigated against three different cancer cell lines, and their selectivity was verified on mesenchymal stem cells. Compounds 1 and 2 displayed selective and high cytotoxicity against human lung and breast cancer cells and showed moderate cytotoxicity against colon cancer cells. Accordingly, they might be auspicious candidates for future pharmacological investigations in lung and breast cancer research. Four (H2XQ)2PdCl4 complexes (H2XQ = 8-hydroxyquinolinium cation and its derivatives) were synthesized and characterized by structure analysis, IR, UV-VIS, NMR and elemental analyses, and their interaction to DNA, antitumor, antimicrobial and antiradical activities were evaluated. Display omitted •Four hybrid organic-inorganic complexes were synthesized and characterized.•They are selectively cytotoxic against A549, HCT116 and MDA-MB-231 cells.•Complexes exhibit high antimicrobial efficacy.•The radical scavenging experiments reveal relatively low antioxidant properties.•The complexes interact with DNA via an intercalation mode.