Objective To investigate the effect of Panlongqi Tablet on the silent information regulator type 1 (SIRT1)/nuclear factor- kappa B (NF- κB) pathway and chondrocyte apoptosis in osteoarthritis (OA) mice. Methods A mouse model of OA was established by surgical resection of the medial meniscus and the anterior cruciate ligament of the right knee, and the mice were divided into normal control group, model group, positive control group, and low- , middle- , and high- dose Panlongqi Tablet groups. Safranin O- fast green staining was performed to observe the changes of knee joint structure; Mankin score was used to evaluate the severity of arthritis; flow cytometry was used to measure chondrocyte apoptosis index; qRT- PCR was used to measure the mRNA expression levels of Bax, Bcl- 2, and caspase- 3, and Western blot was used to measure the protein expression levels of SIRT1 and NF- κB. Results Compared with the normal control group, the model group had significant increases in the apoptosis rate of knee articular chondrocytes, the mRNA expression levels of Bax and caspase- 3, and the protein expression level of NF- κB, as well as significant reductions in the mRNA expression level of Bcl- 2 and the protein expression level of SIRT1 (P<0.05). Compared with the model group, the positive control group and the low- , middle- , and high- dose Panlongqi Tablet groups had significant reductions in the apoptosis rate of knee articular chondrocytes, the mRNA expression levels of Bax and caspase- 3, and the protein expression level of NF- κB, as well as significant increases in the mRNA expression level of Bcl- 2 and the protein expression level of SIRT1 (P<0.05), and Panlongqi Tablet exerted an effect in a dose- dependent manner. Conclusion Panlongqi Tablet can inhibit the apoptosis of knee articular chondrocytes in OA mice, possibly by regulating the SIRT1/NF- κB signaling pathway.