In order to analyze the effect of lateral alkyl on the moisture and heat- humidity resistance of polyester polyurethane (PU), poly3-methyl-1, 5-pentanediol adipate (P2010), poly2-butyl-2-ethyl-1, 3-propylene glycol ester (PBEPG), polyhexadipate diol (CMA2066) and polycaprolactone diol (PCL220N) were used as soft segment to prepare PU materials, respectively. FT-IR, DMA, TG and water contact angle analysis show that side alkyl can improve the microphase separation degree between soft and hard PU segments, reduce the glass transition temperature of soft segments, increase the contact angle with water, and improve the moisture and heat resistance. Two tan δ peaks are observed in the soft and hard segments of PBEPG-PU with butyl and ethyl bilateral alkyl groups. The tensile strength is 22.2MPa and the surface hydrophobicity is strong. The tensile strength retention rate is 71.2% after aging at 100 ℃ and 100 RH for 60 h. It shows good resistance to moisture and heat, and high mechanical strength.