Placenta-specific protein 1 (PLAC1) is considered to play a pivotal role in cancer progression. Here, we investigated the role of PLAC1 in the growth and motility of bladder cancer (BCa) cells. Database analysis and Immunoblot assays were conducted to determine PLAC1 expression in BCa tissues and its correlation with patient prognosis. Furthermore, wound healing, transwell and tube formation assays were performed to evaluate cell motility and angiogenic potential, and the underlying mechanism via which PLAC1 knockdown inhibits BCa progression in vitro was investigated. The data revealed that PLAC1 was obviously overexpressed in BCa tissues and was associated with poor patient prognoses. Additionally, silencing PLAC1 led to reduced viability, migratory capacity, invasion potential and angiogenesis of BCa cells, including T24 and UMUC3 cells. Further investigation showed that PLAC1 knockdown modulated the phosphoinositide 3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FOXO3a) axis by enhancing the phosphorylation of FOXO3a while suppressing the phosphorylation of PI3K as well as Akt. Moreover, we demonstrated that the inhibition of BCa progression by PLAC1 knockdown was primarily mediated through the targeting of FOXO3a. In summary, these findings confirmed the potential of PLAC1 as a promising target for suppressing BCa growth by elevating FOXO3a levels and modulating the PI3K/Akt/FOXO3a signaling axis.