Objective To investigate the roles of transforming growth factor-beta 1 (TGF-β1), procollagen I C-terminal propeptide (PICP), N-terminal procollagen III propeptide (PIIINP), hyaluronic acid (HA), and laminin (LN) in the development of hydrocephalus after hemorrhage in the cerebrospinal fluid system.Methods The patients with traumatic brain injury and spontaneous intracranial hemorrhage (involving the subarachnoid space and the ventricular system) who were treated in our hospital were enrolled, and the levels of TGF-β1, PICP, PIIINP, HA, and LN in cerebrospinal fluid were measured at different time points after admission. The patients were followed up to observe the development of hydrocephalus within half a year, and the levels of TGF-β1, PICP, PIIINP, HA, and LN in cerebrospinal fluid were compared between the patients with hydrocephalus and those without hydrocephalus. The correlation of TGF-β1 with PICP, PIIINP, HA, and LN expression and their time-concentration relationship were analyzed.Results A total of 83 patients were enrolled, and after the follow-up for half a year, 53 patients did not have hydrocephalus (group A) and 30 had hydrocephalus (group B). Group B had significantly higher levels of TGF-β1, PICP, HA, and LN in cerebrospinal fluid than group A at all time points. In all patients, TGF-β1 was positively correlated with PICP, PIIINP, HA and LN (r=0.8248, 0.7951, 0.9078, and 0.7572). TGF-β1 in cerebrospinal fluid reached the highest level on day 7 and then gradually decreased, while the expression of PICP, PIIINP, HA, and LN started to increase rapidly when TGF-β1 reached the highest level and then slowly decreased.Conclusions TGF-β1, PICP, PIIINP, HA, and LN in cerebrospinal fluid play important roles in the development of chronic hydrocephalus after hemorrhage in the cerebrospinal fluid system, and TGF-β1 may promote the expression of PICP, PIIINP, HA, and LN.