Endometrial cancer (EC) is one of the most common gynecological malignant tumors. Further investigation of the potential molecular mechanism of EC is important. Small nucleolar RNA (snoRNA) is a type of non-coding RNA, with an unclear biological function in EC. We found that Box C/D snoRNA SNORD3B-2 participated in EC oncogenesis and development via the PI3K-AKT signaling pathway. RNA immunoprecipitation (RIP) revealed that SNORD3B-2 bound to polo-like kinase 1 (PLK1) through fibrillin (FBL). RTL-P (reverse transcription at low dNTPs-PCR) and actinomycin D assays confirmed that SNORD3B-2 directed 2′-O-methylation modification of PLK1 mRNA, and the modification could promote the stability of PLK1 mRNA which could mediate tumor growth and metastasis in EC. Moreover, SNORD3B-2 overexpression was associated with retained Exon 3 of RAB17 thus activating the PI3K-AKT signaling pathway. This alternative splicing was achieved by SNORD3B-2 regulating the protein level of splice factor SF3B1 (splicing factor 3b subunit 1).