As small non-coding RNAs, MicroRNAs (miRNAs) bind to the 3′ untranslated region (3′-UTR) of mRNA targets to control gene transcription and translation. The gene of miR-330 has two miRNA products, including miR-330-3p and miR-330-5p, which exhibit anti-tumorigenesis and/or pro-tumorigenesis effects in many kinds of malignancies. In cancers, miR-330-3p and miR-330-5p aberrant expression can influence many malignancy-related processes such as cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition, as well as angiogenesis and responsiveness to treatment. In many cancer types (such as lung, prostate, gastric, breast, bladder, ovarian, colorectal, and pancreatic cancer, and osteosarcoma), miR-330-5p acts as an anti-tumor agent. These cancers have low levels of miR-330-5p that leads to the upregulation of the tumor promotor target genes leading to tumor progression. Here, overexpression of miR-330-5p using miRNA inducers can prevent tumor development. Dual roles of miR-330-5p have been also indicated in the thyroid, liver and cervical cancers. Moreover, miR-330-3p exhibits pro-tumorigenesis effects in lung cancer, pancreatic cancer, osteosarcoma, bladder cancer, and cervical cancer. Here, downregulation of miR-330-3p using miRNA inhibitors can prevent tumor development. Demonstrated in breast and liver cancers, miR-330-3p also has dual roles. Importantly, the activities of miR-330-3p and/or miR-330-5p are regulated by upstream regulators long non-coding RNAs (lncRNAs), including circular and linear lncRNAs. This review comprehensively explained miR-330-3p and miR-330-5p role in development of cancers, while highlighting their downstream target genes and upstream regulators as well as possible therapeutic strategies.