Objective To investigate the induction of autophagy of MDA-MB-468 cells in triple-negative breast cancer (TNBC) by sericin through regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, and to clarify the target of action. Methods MDA-MB-468 cells were randomly divided into a control group (without drugs), an experimental group (8 mg·mL ^-1 sericin), and an Akt activator group (8 mg·mL ^-1 sericin + 10 μmol·L ^-1 SC79). After 24 hours treatment with corresponding drugs, the mRNA expression levels of PI3K, Akt, mTOR, autophagy effector protein (Beclin1), autophagy associated protein 5 (ATG5), microtubule associated light chain protein3 (LC3) and chelator 1 (P62) in cells of each group were detected by RT qPCR. The protein expression levels of PI3K, Akt, p-Akt, mTOR, p-mTOR, Beclin1, ATG5, LC3 and P62 in cells of each group were detected by Western blotting. The localization and fluorescence intensity of LC3 and P62 proteins in cells of each group were detected by immunofluorescence staining. Results Compared with the control group, the mRNA levels of PI3K, Akt, mTOR, and P62 and the protein levels of PI3K, Akt, p-Akt, mTOR, p-mTOR, and P62 in MDA-MB-468 cells of the experimental group were significantly decreased (P<0.05), while the mRNA levels of Beclin1, ATG5, LC3 and the protein levels of Beclin1, ATG5, LC3Ⅱ/LC3Ⅰ were significantly increased (P<0.05). Compared with the experimental group, the mRNA levels of PI3K, Akt, mTOR, P62 and the protein levels of PI3K, Akt, p-Akt, mTOR, p-mTOR, P62 in MDA-MB-468 cells of the Akt activator group were significantly increased (P<0.05), while the mRNA levels of Beclin1, ATG5, LC3 and the protein levels of Beclin1, ATG5, LC3Ⅱ/LC3Ⅰ were significantly decreased (P<0.05). Conclusion The induction effect of sericin on autophagy of MDA-MB-468 cells can be achieved by targeting Akt to regulate the transduction of the PI3K/Akt/mTOR signaling pathway.