RNA-targeted therapies have emerged as a revolutionary breakthrough in biomedicine recently, offering unprecedented precision in regulating gene expression. Among these, steric blocking oligonucleotides (SBOs) represent a unique class of therapeutics that function through a steric blocking mechanism, allowing for reversible effects without RNA degradation. However, designing SBOs is challenging due to the lack of universal guidelines and the need for detailed analysis of mRNA/pre-mRNA characteristics, key site distributions, and RNA-binding protein interactions. To address this, we developed a novel aptamer-based technology called translation inhibition RNA (tiRNA), which inhibits mRNA translation by linking an eIF4G-targeting aptamer to a reverse complementary sequence of the target gene's 5′-UTR. This approach leverages the typical translation initiation mechanism of mRNA and employs a straightforward design strategy to specifically target and inhibit the translation of selected mRNAs without affecting others or causing RNA degradation. The efficacy of tiRNA is comparable to that of siRNA, providing precision, safety, and controllability for treating diseases linked to protein overexpression. Moreover, the effects of tiRNA can be reversed using a specially designed neutralizing strand, restoring normal mRNA translation and enhancing treatment controllability and personalization. This method holds significant potential for applications in cancer, gene therapy, and other fields requiring precise regulation of protein expression.