Renal cell carcinoma (RCC) remains one of the most lethal urinary tumors in East Asia despite great advancements in treatment strategies in recent years. Ribosomal protein S20 (RPS20) is considered a new oncogene; however, little information is available on its expression, regulation and biological function in patients with RCC. In the present study, 43 pairs of human RCC and neighboring normal renal tissues were examined for protein expression and immunohistochemistry examination of RPS20. Lentiviral transduction was also employed to create RPS20 knockdown cell lines for downstream cellular experiments. MTT, flow cytometry, wound healing, colony formation and invasion assays were used to examine how RPS20 affected kidney renal clear cell carcinoma (KIRC) cell behavior. Western blotting was used to detect cycle‑related proteins (CDK4 and cyclin D1), Wnt‑related proteins (N‑cadherin and E‑cadherin) and signaling proteins [phosphorylated (p)‑AKT and p‑ERK]. The functions of RPS20 were examined in 786‑O cells with RPS20 knockdown. RPS20 was significantly overexpressed in tumor tissues compared with its expression in the corresponding normal tissues. RPS20 expression was linked to tumor stage, differentiation grade, tumor size and lymph node metastasis, and it had an independent prognostic value in KIRC. Since RCC cell proliferation, migration and invasion were suppressed when RPS20 was knocked down, the formation of renal tumors was markedly slowed down. In RPS20 knockdown cell lines, CDK4, cyclin D1 and E‑cadherin were downregulated, while N‑cadherin expression was increased. RPS20 was also observed to be involved in controlling the activation of the ERK and mTOR signaling pathways. In summary, the present study showed that RPS20 increased cell proliferation in RCC by activating the AKT‑mTOR and ERK‑MAPK signaling pathways, which suggests that RPS20 may be a therapeutic and prognostic target for RCC.