Objective To construct the lentivirus vector targeting human protein kinase R-like endoplasmic reticulum kinase (PERK) gene, and to study the effect of lentivirus modification of human PERK gene on endoplasmic reticulum(ER) stress-mediated apoptosis in C2C12 cells. Methods Primer pairs of PERK gene were designed and synthesized. Human PERK gene was amplified by PCR from the expression plasmid pCDNA3.l (-)-PERK and was cloned into pWPT-GFP lentivirus vector. Then the recombinant PERK lentivirus were produced in 293T cells following co-transfection between pWPT-GFP-PERK and the lentivirus packaging plasmids pMD2G, pSPAX2. The supernatants were collected 48 h after transfection and myoblast C2C12 were infected in vitro. Infection efficiency of green fluorescent protein (GFP) was observed. The effect of recombinant lentivirus PERK on proliferation and apoptosis in C2C12 cells was detected by flow cytometry (FCM) in ER stress. Western blotting analysis was used to examine the expression of apoptosis-related proteins Cleaved Caspase-3 and Chop. Results The recombinant lentivirus PERK was successfully constructed, with a titer of 4.2×10⁸ efu/mL. FCM analysis showed that under ER stress condition, the ratio of G₁ phase C2C12 cells in the TM+LV-PERK group (54.37 %) was significantly lower than those in the TM group (77.91%) and LV-GFP (66.41%, P<0.05); the ratio of S phase C2C12 cells in the TM LV-PERK group (31.36%) was significantly higher than those in the TM group (12.14%) and LV-GFP (16.96%, P<0.05). The apoptosis rate in the TM LV-PERK group(25.91%) was significantly higher than those in the TM group (11.79%) and Ad-GFP group (11.24%, P<0.05). Western blotting analysis showed that the expression of Cleaved Caspase-3 and Chop protein was consistent with the results of FCM. Conclusion We have successfully constructed and packaged recombinant lentivirus PERK. Under ER stress condition, LV-PERK can promote the proliferation and apoptosis in C2C12 cells.