A modified cooperative fuel research (CFR) octane rating engine and a constant-volume combustion chamber (CVCC) (CID510) were adopted to investigate the effect of the addition of polyoxymethylene dimethyl ether (PODE) on the ignition characteristics of diesel fuels. PODE was blended in diesel fuel with a volume fraction from 0 to 30%. The ignition delay times of PODE/diesel blends were obtained on a CVCC at a temperature of 833-893 K, and a reduction of environmental oxygen (O-2) content ranges from 21 to 12.8%. With PODE addition, the ignition delay time decreases, whereas the onset of low-temperature heat release (LTHR) moves forward and the peak of LTHR increases. The blends with a higher PODE fraction can weaken the negative effect on ignition delay caused by the reduction of oxygen content in air. The critical compression ratio (CCR) and the apparent heat release rate of binary blends were measured on the CFR engine at an equivalence ratio of 0.5 under homogeneous charge compression ignition combustion mode. The CCR becomes lower with higher PODE content in the blend. All blends exhibited two-stage ignition. The blends with a higher PODE fraction give a higher percentage of LTHR Numerical simulation reveals that decomposition of PODE produces more CH2O, which accelerates the low-temperature reaction. The reactions related to O-center dot and O-2 are enhanced by oxygen available in PODE, which, along with the molecular structure of PODE, results in higher reactivity for the PODE/diesel binary blends.