〔Abstract〕 Objective To analyze the effects of family participation in nursing guidance on physical and mental development, nutritional status and immune function of premature infants. Methods A total of 86 premature infants delivered in Henan Children's Hospital from March 2017 to March 2019 were selected and randomly divided into a control group and an observation group, with 43 infants in each group. The control group received routine nursing, and the observation group received home nursing instruction, and the contents of serum C-reactive protein, globulin, immunoglobulin (Ig) M, albumin, IgA, IgG, average daily increase quality, intelligence, and neurodevelopment of the two groups of premature infants were observed after nursing. Results The contents of globulin, albumin, IgA, IgM and average daily weight increase of premature infants in the observation group were higher than those in the control group, while the content of C-reactive protein was lower than that in the control group, the differences were statistically significant (P < 0.05). The scores of neonatal behavior nervous system assessment (NBNA), psychomotor development index (PDI) and intelligence development index (MDI) of premature infants in the observation group were higher than those in the control group at 1, 3 and 6 months after discharge, and the differences were statistically significant (P < 0.05). Conclusion Home nursing guidance can strengthen the nutritional status of preterm infants, improve the body's immune function, and effectively improve physical and intellectual development.