Hepatitis C virus (HCV) infection is still a significant global health problem despite therapeutic advancements. Ribavirin and interferon therapy have been the sole available treatments for HCV infection for a number of years with low efficacy. Thus, currently, a number of therapeutic strategies are being used, including nanoparticles (NPs), micro‐RNAs such as small interfering RNA (siRNA), RNAi‐based gene silencing and antisense oligonucleotide‐based microRNA‐122, microRNA‐155, and short hairpin RNAs (shRNAs), and immunotherapeutic approaches such as anti‐programmed cell death 1(PD‐1), monoclonal antibodies (mAb or moAb), and monocyte‐derived dendritic cells (Mo‐DCs). Furthermore, direct‐acting antivirals (DAAs) and host‐targeting agents (HTA) were also the current therapeutic approaches with great efficacy. In spite of different clinical trials on HCV vaccine developments, nowadays there is no effective HCV vaccine in opposition to virus due to various challenges including genetic diversity, lack of immunocompetent small animal models, shortage of HCV vaccination testing alternatives, lack of an effective tissue culture method for replicating HCV, and inadequate knowledge regarding to immune responses against HCV infection. Nowadays, mRNA vaccine, recombinant viral vector, peptides vaccine, virus‐like particles, DNA vaccine, rational designed vaccine, and recombinant polyantigenic T‐cell‐based vaccine are novel promising candidates for HCV vaccine based on various clinical trials. This review summarizes the different therapeutic approaches and the advancements of vaccine candidates for HCV infection.