The plateau zokor (Myospalax baileyi) is a specialized subterranean rodent living on the Qinghai-Tibet Plateau, which is short of oxygen in burrows. In general, hypoxia can induce apoptosis. In order to shed lights into the molecular mechanism of the plateau zokor adaptation to the hypoxic environment, the sequences of Pidd, Fas, Bax, Puma, Apaf-1, Scotin, Perp, Igfbp3 and Bcl-2 were analyzed by MEGA 7.0, PAML4.8 program and Ancestor program. In addition, the expression levels of these genes were determined with real-time PCR in the lung tissues of zokors inhabiting at different altitudes (3 300 m and 2 260 m) and compared with the SD rats in this study. The sequences of the apoptotic target genes in plateau zokors were highly homologous those of Nannospalax galili (Table 2 and Table 3). PIDD (Fig. 2), PUMA (Fig. 3), Apaf-1 (Fig. 4), IGFBP3 (Fig. 5) and BCL-2 (Fig. 6) in plateau zokor and Nannospalax galili showed convergent sites in their functional domains. The SIFT test showed that, compared to other species, 78, 853, 157, 320 and 285 variation sites of plateau zokor and Nannospalax galili had effects on the function of p53, PIDD, PUMA, Apaf-1 and IGFBP3, respectively (Table 5). At the high altitude (3 300 m), the expression levels of proapoptotic genes Pidd, Bax and Puma were significantly decreased, while the expression level of antiapoptotic gene Bcl-2 was significantly increased; instead, the expression levels of proapoptotic and antiapoptotic genes showed no significant difference in SD rats. The expression levels of apoptotic genes in plateau zokor were higher than in the SD rats (Fig. 7, 8). At the high altitude (3 300 m), the ratio of Bcl-2/Bax expression was significantly increased in plateau zokor, whereas that of the SD rat was not (Fig. 9). The results above suggested that site variation of p53 in plateau zokor resulted in different expression patterns of p53 targeted apoptotic genes from those in SD rat: the expression levels of proapoptotic genes Pidd, Bax, Puma and Apaf-1 were decreased, while the expression level of antiapoptotic gene Bcl-2 was increased, so as to inhibit apoptosis under hypoxic environment. Under the long-term hypoxia conditions, the p53 targeted proteins PIDD, PUMA, Apaf-1 and IGFBP3 had significant variation sites, which might alter their ability to combine with their functional complexes and inhibit apoptosis. Therefore, over the long-term hypoxia adaptation, the apoptotic genes of plateau zokor underwent structural variation, leading to change in the expression levels of these genes, and thereby inhibited apoptosis, which is one of the molecular mechanisms of plateau zokor adaption to the hypoxic burrowing environment.