Tissue resident memory T cells provide effective tissue surveillance and can respond rapidly to infection leading to the elimination of pathogens. Recently, efforts to develop vaccination strategies aimed at generating Trm cells have been increasing. Animal vaccine studies have shown promising results targeting Trm responses at barrier sites such as lung, female reproductive tract, and liver. However, only a few studies have investigated the effect of adjuvants on the formation of Trm cells induced by those vaccination strategies. We have previously shown that the choice of adjuvant utilised for subunit CD8 T cell immunisation strongly influences subsequent liver CD8 Trm cell formation. In this study, we assessed the ability of a broad range of adjuvants with different stimulatory characteristics to promote the induction of murine liver Trm cells, in the context of subunit immunisation. The adjuvants investigated included: i) LPS, a TLR4 ligand; ii) agonists of the endosomal receptors TLR3, TLR7 and 3 types of TLR9 ligands; and iii) ligands of the cytosolic receptors cGAS and RIG‑I. Results showed that in mice the TLR9 agonist CpG B-P a type of CpG that combines a murine B class and a P class oligodeoxynucleotide, and CpG 2006 (also known as CpG 7909), a human B class CpG, exhibited superior Trm enhancement capability compared to the other adjuvants. It was also determined that the transfection reagent DOTAP enhances the formation of liver Trm cells mediated by the each one of the three CpG tested. Importantly, in vaccination studies against malaria, we were able to show that the use of CpG 2006 complexed with DOTAP induced high numbers of P. berghei-specific Trm cells which enable high levels of sterile protection against sporozoite challenge. These studies lay the foundations for the generation of an efficient liver Trm-based malaria vaccine and the potential for translation.