Objectives  Our clinical trial started around the "two-hit" hypothesis, compared and analyzed the low birth weight rates and progesterone utilization rates during early-pregnancy in patients with different types of hypospadias, because of “low birth weight” and “progesterone utilization during early pregnancy” are reasonable representations of “gene susceptibility” and “endocrine disruptor”, so to discuss the etiology of hypospadias through this way.Methods   According to the information from the registration forms of 97 boys firstly enrolled between May 2012 to December 2013 at the urological department of Soochow University affiliated children’s hospital, and all these patients had met criteria of this trial, we divided them in to different groups due to the position of urethral orifice, generating the data of low birth weight rates and progesterone utilization rates in each group, and then used SPSS statistical software to do chi-square test and Kendall, Spearman rank correlation analysis . Results  Pearson X2 = 12.160, P <0.05 could confirm that there existed a differential distribution of low birth weight rates in groups with different types of hypospadias from the aspect of statistics, π = 0.332, P <0.01; rs = 0.350, P= <0.01, could confirm that there existed a rank correlation of low birth weight rates in groups with different types of hypospadias from the aspect of statistics, which was the higher rate in the group, the severer of the patients in it ; Pearson X2 = 11.004, P <0.05, could confirm that there existed a differential distribution of progesterone utilization rates in groups with different types of hypospadias from the aspect of statistics, π = 0.304, P<0.01; rs = 0.320, P<0.01, could confirm that there existed a rank correlation of progesterone utilization rates in groups with different types of hypospadias from the aspect of statistics, which was the higher rate in the group, the severer of the patients in it. Conclusions The existing differential distribution and rank correlation of low birth weight rates in groups with different types of hypospadias elucidated the first part of the "two-hit" hypothesis, which is that hypospadias needs “gene susceptibility” ; The existing differential distribution and rank correlation of progesterone utilization during early pregnancy in groups with different types of hypospadias elucidated the second part of the "two-hit" hypothesis, which is that besides gene susceptibility, hypospadias also needs particular environments exposure during the early stage of human embryonic development.